CN113419073B - High-flux full-automatic microfluidic fluorescence immunoassay device - Google Patents
High-flux full-automatic microfluidic fluorescence immunoassay device Download PDFInfo
- Publication number
- CN113419073B CN113419073B CN202010235482.4A CN202010235482A CN113419073B CN 113419073 B CN113419073 B CN 113419073B CN 202010235482 A CN202010235482 A CN 202010235482A CN 113419073 B CN113419073 B CN 113419073B
- Authority
- CN
- China
- Prior art keywords
- joint inspection
- washing
- clamping
- reaction tube
- linear slide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000003018 immunoassay Methods 0.000 title claims abstract description 14
- 238000007689 inspection Methods 0.000 claims abstract description 137
- 238000006243 chemical reaction Methods 0.000 claims abstract description 122
- 238000005406 washing Methods 0.000 claims abstract description 95
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 84
- 239000008280 blood Substances 0.000 claims abstract description 60
- 210000004369 blood Anatomy 0.000 claims abstract description 50
- 238000003860 storage Methods 0.000 claims abstract description 31
- 238000002347 injection Methods 0.000 claims abstract description 30
- 239000007924 injection Substances 0.000 claims abstract description 30
- 238000001917 fluorescence detection Methods 0.000 claims abstract description 21
- 239000007788 liquid Substances 0.000 claims description 124
- 238000005070 sampling Methods 0.000 claims description 30
- 239000002699 waste material Substances 0.000 claims description 21
- 238000004891 communication Methods 0.000 claims description 11
- 239000012530 fluid Substances 0.000 claims description 10
- 239000003550 marker Substances 0.000 claims description 10
- 230000009471 action Effects 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 239000006210 lotion Substances 0.000 abstract description 10
- 238000012546 transfer Methods 0.000 abstract description 10
- 238000003759 clinical diagnosis Methods 0.000 abstract description 2
- 238000001514 detection method Methods 0.000 description 27
- 238000000034 method Methods 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 238000007405 data analysis Methods 0.000 description 4
- 238000007599 discharging Methods 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011358 absorbing material Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000033764 rhythmic process Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 238000001746 injection moulding Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1004—Cleaning sample transfer devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
- G01N2035/0401—Sample carriers, cuvettes or reaction vessels
- G01N2035/0437—Cleaning cuvettes or reaction vessels
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The invention relates to a high-flux full-automatic microfluidic fluorescence immunoassay device, which can comprise: the joint inspection integrated reagent card is provided with a plurality of parallel joint inspection reaction tubes; the rotary table is provided with a plurality of storage tanks, and each storage tank is used for storing one joint inspection integrated reagent card; the whole blood automatic sample injection device is used for adding a whole blood sample to be detected into the joint inspection reaction tube; the joint inspection integrated reagent card transfer device comprises a mechanical arm, a plurality of clamping jigs, a linear slide rail and a propelling device, wherein the clamping jigs are slidably arranged on each station of the linear slide rail; the centrifugal reactor is arranged beside the reaction station of the linear slide rail; the lotion filling device is arranged beside a lotion filling station of the linear slide rail; the centrifugal washing device is arranged beside a washing station of the linear slide rail; and the fluorescence detection device is arranged beside the fluorescence detection station of the linear slide rail. The device has simple structure and high degree of automation, can carry out multi-index arbitrary combination joint inspection, and fully meets the clinical diagnosis requirement.
Description
Technical Field
The invention relates to the field of blood analysis devices, in particular to a high-flux full-automatic microfluidic fluorescence immunoassay device.
Background
In medical diagnostics, health care, food safety, and other emergency settings, automated, high-sensitivity, point-of-care detection has always been a real-time, vigorous need.
At present, the label immunity instant detection based on lateral chromatography is widely applied, and the label relates to colloidal gold, fluorescence, lanthanide rare earth elements Eu2+, quantum dots and the like. The method has the greatest advantages of simple and convenient detection operation, and the used instrument structure is relatively short, so that the method can meet the instant detection requirements of a plurality of places. The lateral chromatography-based labeled immunoreagent material has poor quality controllability, large uncertainty of production process control, unstable quality of reagent assembly materials and uncontrollable detection process, and the detection result has low sensitivity and large variation, and is easy to occur in clinical application, so that the lateral chromatography-based labeled immunoreagent material is only used for screening detection of high-risk groups.
Other forms of instant detection include single-person integrated magnetic particle solid phase chemiluminescent immunoassay, microfluidic disc-mode instant detection, and the like, which are also under development and application in the same period. However, the method is complicated in terms of simplicity and convenience of analysis compared with the method for detecting the marker immunity of the lateral chromatography in real time, the reagent and instrument components all need more operation and auxiliary conditions, the detection flux is low, the reagent detection cost is relatively high, the degree of satisfaction of the actual application scene is poor, and the medical economic cost is increased.
Considering that in medical diagnosis applications, most disease diagnoses are combined by a plurality of indexes, and mutual verification is performed to assist disease diagnosis so as to avoid missing diagnosis or misdiagnosis and increase the accuracy of diagnosis; meanwhile, multi-index parallel detection is also used for clinically distinguishing and diagnosing diseases, so that the development of instant diagnosis of multi-index combined detection has important practical requirements.
Marker immunodetection based on lateral chromatography takes two means for this to meet this need: 1>; the method comprises the steps of sequentially separating different detection items on the same nitrocellulose solid-phase membrane (NC membrane), layering and stacking markers of different items, wherein during detection, the samples penetrate into a marker storage position from top to bottom to be combined with corresponding labeled antigens or antibodies, enter the NC membrane through a contact area with the NC membrane, migrate to a solid-phase area through capillary action to be secondarily combined and deposited with solid-phase components to form a visible characteristic detection zone, and the defects are that the different items possibly have mutual interference, particularly, the corresponding antigens and antibodies of one molecule cannot be detected simultaneously, and meanwhile, the detection index number is limited; 2, preparing the different items into independent detection strips, and then respectively placing the independent detection strips into different clamping grooves in the same plastic card, sharing a sample adding pool or respectively and independently adding samples. Due to the technical principle defect of lateral chromatographic marker immunodetection, the detection performance of the two modes cannot be improved or even reduced.
Undoubtedly, people expect a more sensitive and simple method for simultaneously detecting multiple items and marking immunity and instant detection to meet the real needs.
Disclosure of Invention
The invention aims to provide a high-flux full-automatic microfluidic fluorescence immunoassay device so as to solve the problems. For this purpose, the invention adopts the following specific technical scheme:
A high-throughput fully-automatic microfluidic fluorescent immunoassay device, which may comprise:
The joint inspection integrated reagent card is provided with a plurality of parallel joint inspection reaction tubes, and the joint inspection reaction tubes are integrally injection molded;
The rotary table is provided with a plurality of storage tanks, and each storage tank is used for storing one joint inspection integrated reagent card;
The whole blood automatic sampling device is used for adding a whole blood sample to be detected into the joint inspection reaction tube;
The joint inspection integrated reagent card transferring device comprises a mechanical arm, a plurality of clamping jigs, a linear slide rail and a pushing device, wherein the clamping jigs are slidably arranged on each station of the linear slide rail and used for clamping the joint inspection integrated reagent card, the mechanical arm is used for transferring the joint inspection integrated reagent card from the turntable to a feeding station of the linear slide rail, and the pushing device is used for pushing and transferring the joint inspection integrated reagent card along each station in sequence;
The centrifugal reactor is arranged beside the reaction station of the linear slide rail and is used for carrying out centrifugal reaction on the blood sample in the joint inspection reaction tube;
The washing liquid filling device is arranged beside a washing liquid filling station of the linear slide rail and is used for pushing and filling a specified volume of washing liquid into the joint inspection reaction tube;
The washing liquid filling device is arranged beside a washing station of the linear slide rail and is used for repeatedly washing the joint inspection reaction tube in a through mode through centrifugal force;
and the fluorescence detection device is arranged beside the fluorescence detection station of the linear slide rail and is used for carrying out fluorescence detection on the blood sample in the joint inspection reaction tube.
Further, the joint inspection integrated reagent card comprises an upper cover and a base, wherein the upper cover and the base are combined together in a jogged mode and are provided with a lotion injection port and a plurality of blood sample injection ports; the base is sequentially provided with a washing liquid storage tank, a plurality of sample loading liquid guide structures, a reaction tube mounting seat and a waste liquid storage tank along the flowing direction of the reagent; the washing liquid storage tank is communicated with the washing liquid injection port; the joint inspection reaction tube is fixedly inlaid in the reaction tube mounting seat and is provided with a slit-shaped inner cavity, two ends of the inner cavity are respectively provided with a liquid inlet and a liquid outlet, a characteristic marker membrane is arranged at the liquid inlet, and the liquid outlet is in fluid communication with the waste liquid storage tank; the sample loading liquid guide structures are independent, each sample loading liquid guide structure corresponds to one joint inspection reaction tube and one blood sample injection opening respectively, the sample loading liquid guide structures are communicated with the blood sample injection openings, one end of each sample loading liquid guide structure is communicated with the washing liquid storage tank, and the other end of each sample loading liquid guide structure is communicated with the joint inspection reaction tube.
Still further, the loading liquid guide structure comprises a lotion diversion channel and a liquid guide cavity, wherein one end of the liquid guide cavity is in fluid communication with the lotion storage tank through the lotion diversion channel, and the other end of the liquid guide cavity is in communication with the liquid inlet.
Still further, the cross section of the inner cavity is circular, semicircular, elliptic, rectangular or trapezoidal.
Further, the wall surface of the inner cavity can be provided with an arc-shaped or other geometric protruding structure so as to increase the wall surface area of the inner cavity.
Furthermore, grooves are formed in four side faces of the joint inspection integrated reagent card and serve as clamping positions of the clamping jig.
Further, the washing liquid injection port and the blood sample injection port are both in a cross-shaped capping open and closed structure.
Still further, the waste reservoir is in fluid communication with the outlet through a canyon.
Furthermore, the reaction tube mounting seat is provided with a clamping edge which is used for fixing the joint inspection reaction tube.
Furthermore, the joint inspection reaction tube is formed by integrally injection molding PS plastic.
Further, the whole blood automatic sampling device comprises a whole blood mixing device, a whole blood sample sampling device, a needle washing device, a sample pipe rack and a radio frequency sample information collector, wherein the whole blood mixing device is used for taking a test tube filled with a whole blood sample to be detected from the sample pipe rack and carrying out rotary mixing so as to mix the whole blood sample to be detected, the whole blood sample sampling device is used for collecting a whole blood sample with a specified volume and adding the whole blood sample into the joint inspection reaction tube, the needle washing device is used for washing a sampling needle of the whole blood sample sampling device, and the radio frequency sample information collector is used for reading the serial number of the sample pipe and identifying the number of items to be detected and specific varieties of the sample pipe.
Further, the clamping jigs are in driving connection with the first motor through a connecting rod mechanism, so that the clamping and the loosening can be simultaneously realized under the action of the first motor.
Still further, the pushing device comprises a second motor and a third motor, wherein the second motor is used for driving the clamping jig to reciprocate along the linear sliding rail, and the third motor is used for driving the clamping jig to reciprocate transversely to the linear sliding rail.
Further, the centrifugal reactor comprises a driving motor, a reaction disc and a reaction disc rotation stopping device, wherein the driving motor is connected with the reaction disc in a driving mode, a clamping device is arranged on the reaction disc, and the clamping device and the clamping jig are located on the same horizontal plane, so that the joint inspection integrated reagent card can be transferred between the clamping device and the clamping jig under the action of the pushing device, and the reaction disc rotation stopping device is used for preventing the reaction disc from rotating.
Still further, the lotion dispensing device comprises a lotion bottle, a pump, a conduit, a control valve and a dispensing head, the lotion bottle, pump and dispensing head being connected together by the conduit, the control valve being mounted on the conduit between the pump and the dispensing head.
By adopting the technical scheme, the invention has the beneficial effects that:
① The one-step injection molding joint inspection reaction tube is adopted, the marker and the washing liquid are integrated, the detection speed is greatly improved, and the real high flux is realized.
② The washing of the joint inspection reaction tube can be automatically completed, and the sensitivity is obviously improved.
③ The integrated reagent reaction and washing device are combined and run in parallel, so that the reaction operation treatment effect and efficiency are greatly improved.
④ The whole device has simple structure and high degree of automation, can perform multi-index arbitrary combined joint inspection, fully meets the clinical diagnosis requirement, and has extremely high use value.
Drawings
For further illustration of the various embodiments, the invention is provided with the accompanying drawings. The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate embodiments and together with the description, serve to explain the principles of the embodiments. With reference to these matters, one of ordinary skill in the art will understand other possible embodiments and advantages of the present invention. The components in the figures are not drawn to scale and like reference numerals are generally used to designate like components.
FIG. 1 is a schematic structural diagram of a high-throughput fully-automatic microfluidic fluoroimmunoassay device according to an embodiment of the present invention;
FIG. 2 is a schematic structural diagram of a joint inspection integrated reagent card of the high-throughput full-automatic microfluidic fluorescence immunoassay device shown in FIG. 1;
fig. 3 is a schematic structural diagram of a centrifugal reactor of the high-throughput fully-automatic microfluidic fluoroimmunoassay device shown in fig. 1.
Detailed Description
The invention will now be further described with reference to the drawings and detailed description.
As shown in fig. 1, a high-throughput full-automatic microfluidic fluorescence immunoassay device may include a joint inspection integrated reagent card 1, a turntable 2, a whole blood automatic sampling device 3, a joint inspection integrated reagent card transfer device 4, a centrifugal reactor 5, a washing liquid filling device 6, a centrifugal washing device 7, a fluorescence detection device 8, and the like. The specific structure and the working procedure of each device are described in detail below.
As shown in fig. 2, the joint inspection integrated reagent card 1 includes a base 11, a cover (not shown), and a plurality of parallel joint inspection reaction tubes 12, each of the joint inspection reaction tubes 12 being for inspecting an item. The base 11 and the upper cover may be integrally injection molded from PP plastic. The upper cover and the base 11 are jogged and combined together to wrap the joint inspection reaction tube 12. The upper cover is provided with a lotion injection port and a plurality of blood sample injection ports which are in a cross-shaped top-sealing opening and closing structure. When the liquid is injected, the washing liquid injection opening and the plurality of blood sample injection openings are propped open by the needle heads, and after the needle heads are withdrawn, the washing liquid injection opening and the plurality of blood sample injection openings are closed, so that liquid leakage during subsequent centrifugal reaction and washing is avoided. The base 11 is provided with a washing liquid storage tank 13, a plurality of sample loading liquid guiding structures 14, a reaction tube mounting seat 15 and a waste liquid storage tank 16 in sequence along the flowing direction of the reagent. Wherein the washing liquid storage tank 13 has a trapezoid cavity structure and is communicated with the washing liquid injection port, so that washing liquid can be added into the washing liquid storage tank 13 through the washing liquid injection port. The washing liquid reservoir 13 may contain a washing liquid sufficient to sufficiently wash the joint inspection reaction tube 12. In one embodiment, the wash tank 13 has a volume of 3mL. The loading liquid guiding structure 14 is positioned between the washing liquid storage tank 13 and the reaction tube mounting seat 15. The plurality of loading and fluid transfer structures 14 are independent, and each loading and fluid transfer structure 14 corresponds to one joint inspection reaction tube 12 and one blood sample injection port. Specifically, each loading liquid guiding structure 14 includes a wash liquid diversion channel 141 and a liquid guiding cavity 142, one end of the liquid guiding cavity 142 is in fluid communication with the wash liquid storage tank 13 through the wash liquid diversion channel 141, and the other end is in communication with the liquid inlet of the joint inspection reaction tube 12. Thus, the wash solution may be introduced from the wash solution distribution channel 141 into the liquid guide chamber 142 by centrifugal force, and further into the joint inspection reaction tube 12.
The joint inspection reaction tube 12 is fixedly embedded in the reaction tube mounting seat 15, specifically, a clamping edge is arranged on the reaction tube mounting seat 15, and the joint inspection reaction tube 12 is fixed through the clamping edge. Therefore, the joint inspection reaction tube 12 does not move during centrifugation. The joint inspection reaction tube 12 can be integrally injection-molded by PS plastic, and has good light transmittance. The joint inspection reaction tube 12 has a slit-shaped inner cavity, and this structure is advantageous in that capillary action is generated to advance the reaction progress. That is, capillary action can be formed in the cavity, which is favorable for the solid-phase process and the drive detection reaction. The cross section of the inner cavity can be round, semicircular, elliptic, rectangular or trapezoidal, etc. The wall surface of the inner cavity is a reaction surface, and the upper surface of the joint inspection reaction tube 12 is an observation surface. Preferably, the wall surface of the inner cavity is provided with a protrusion structure which can be provided with an arc shape or other geometric shapes so as to increase the surface area, namely the area of the reaction surface, and further improve the reaction speed. The joint inspection reaction tube 12 is provided with a liquid inlet and a liquid outlet at two ends, wherein a characteristic marker membrane (not shown) is arranged at the liquid inlet and is in fluid communication with the liquid guide cavity 142 of the loading liquid guide structure 14, so that the characteristic marker on the characteristic marker membrane can be brought into the joint inspection reaction tube 12 by liquid, and the liquid outlet is in fluid communication with the waste liquid storage tank 16.
As shown in fig. 2, the waste reservoir 16 is a flat horseshoe-shaped hollow cavity structure with one end closed. Of course, other configurations of waste reservoir 16 are possible. A waste liquid reservoir 16 is provided at the rear end of the joint inspection reaction tube 12, and is filled with a water absorbing material. The water absorbing material is used for absorbing reaction waste and washing waste liquid so as to avoid backflow. The water absorbing material may be a sponge or a resin, etc. Preferably, the waste reservoir 16 is connected to the outlet of the joint inspection reaction tube 12 through a canyon to avoid backflow of unabsorbed reaction waste and wash solution.
As shown in fig. 2, grooves 17 are provided on four sides of the joint inspection integrated reagent card 1, respectively, and the grooves 17 are used for clamping the joint inspection integrated reagent card 1 during transportation and on the centrifugal reactor 5 and the centrifugal washing device 7.
As shown in fig. 1, the turntable 2 is provided with a plurality of storage tanks, each for storing one joint inspection integrated reagent card 1. The turntable 2 is controlled to rotate by a motor, so that the required joint inspection integrated reagent card 1 can be transferred to a discharging position. The discharging position is close to the joint inspection integrated reagent card transferring device 4, so that the joint inspection integrated reagent card transferring device 4 can take away the joint inspection integrated reagent card 1 positioned on the discharging position.
As shown in fig. 1, the whole blood automatic sampling device 3 may include a whole blood mixing device 31, a whole blood sample sampling device 32, a needle washing device 33, a sample tube rack 34 and a radio frequency sample information collector 35. The radio frequency specimen information collector 35 is used for reading the serial number of the sample tube, and identifying the number of items to be detected and the specific variety. A sample tube holder 34 is positioned below the whole blood mixing device 31 for holding a sample tube containing a whole blood sample. The whole blood mixing device 31 is used for clamping up the sample tube from the sample tube rack 34 and mixing the whole blood sample by rotation. The sampling needle 321 of the whole blood sample sampling device 32 moves onto the sample tube on the whole blood mixing device 31 under the action of the driving motor, pierces the cover and enters the sample tube to extract a whole blood sample with a specified volume, and then moves to the blood sample injection port of the corresponding joint inspection reaction tube 12 of the joint inspection integrated reagent card 1 positioned on the sample injection station, and adds the sample with the specified volume to the joint inspection reaction tube 12. Sampling and loading of the next detection item are continued until sampling of all detection items of the joint inspection integrated reagent card 1 is completed. When the test blood sample is replaced, the sampling needle 321 of the whole blood sample sampling device 32 needs to be washed to prevent cross contamination. The needle washing device 33 may include a first wash bottle 331, a wash tank 332, a wash valve 333, a waste liquid collection bottle 334, a wash sample introduction motor, a waste liquid motor, and corresponding piping, etc. The sampling needle 321 of the whole blood sample sampling device 32 moves into the washing tank 332 of the needle washing device 33, the washing liquid sampling motor and the waste liquid motor are started simultaneously, washing liquid moves and is sprayed out along a pipeline from the first washing liquid bottle 331 to the inner cavity of the sampling needle 321 and the washing liquid nozzle on the side wall of the washing tank 332, the inner wall and the outer wall of the sampling needle 321 are sufficiently washed, the waste liquid is introduced into the waste liquid collecting bottle 334, and the washing liquid valve 333 is used for adjusting the liquid amount, the pressure and the washing rhythm entering the sampling needle 321.
As shown in fig. 1, the joint inspection integrated reagent card transferring device 4 includes a mechanical arm 41, a plurality of clamping jigs 42, a linear slide rail 43 and a pushing device, where the plurality of clamping jigs 42 are slidably mounted on each station (e.g., a sample feeding station, a reaction station, a washing liquid filling station, a washing station, a fluorescence detection station, etc.) of the linear slide rail 43, for clamping the joint inspection integrated reagent card 1. Specifically, the plurality of clamping jigs 42 are in driving connection with the first motor 44 through a link mechanism 45, so as to achieve simultaneous clamping and unclamping under the action of the first motor 44. The clamping fixture 42 comprises clamping arms 421 and clamping teeth 422, and clamps the side grooves 17 of the joint inspection integrated reagent card 1 under the drive of the first motor 44. The mechanical arm 41 is used for transferring the joint inspection integrated reagent card 1 from the turntable 2 to the sample feeding station of the linear slide rail 43. The robot 41 is a multi-axis robot, and the clamping jaw is similar to the clamping jig 42. The pushing device is used for pushing and transferring the joint inspection integrated reagent card 1 along each station in sequence. Specifically, the pushing device includes a second motor 46 and a third motor 47, the second motor 46 is used for driving the clamping jig 42 to reciprocate along the linear slide rail 43 so as to transfer the joint inspection integrated reagent card 1 from one station to the next station, and the third motor 47 is used for driving the clamping jig 42 to reciprocate transversely to the linear slide rail 43 so as to realize pushing the joint inspection integrated reagent card 1 onto the centrifugal reactor 5 and the centrifugal washing device 7 and taking out the joint inspection integrated reagent card 1 from the centrifugal reactor 5 and the centrifugal washing device 7.
As shown in fig. 3, a centrifugal reactor 5 is disposed beside the reaction station of the linear slide 43 for performing a centrifugal reaction on the blood sample in the joint inspection reaction tube 12. Specifically, the centrifugal reactor 5 comprises a driving motor 51, a reaction disc 52 and a reaction disc rotation stopping device 53, the driving motor 51 is in driving connection with the reaction disc 52, a clamping device 54 is arranged on the reaction disc 52, and the clamping device 54 is used for fixing the joint inspection integrated reagent card 1 on the reaction disc 52. The reaction disk rotation preventing means 53 holds the side surface of the reaction disk 52 against rotation. The pushing device of the joint inspection integrated reagent card transferring device 4 drives the clamping jig 42 to transfer the joint inspection integrated reagent card 1 onto the reaction disc 52 and fix the joint inspection integrated reagent card by the clamping device 54, and the reaction disc 52 rotates for a certain time at a specified speed under the driving of the driving motor 51, so that reactants in the joint inspection reaction tube 12 are driven to flow, and the reaction process is accelerated. When the reaction time has elapsed, the drive motor 51 is stopped, and the reaction disk rotation stopping means 53 clamps the side surface of the reaction disk 52 to prevent rotation thereof, and the pushing means of the joint inspection integrated reagent card transferring means 4 drives the clamping jig 42 to take out the joint inspection integrated reagent card 1 from the reaction disk 52. In order to make the joint inspection integrated reagent card 1 smoothly enter and exit the centrifugal reactor 5, the reaction disc 52 (specifically, the clamping device 54) of the centrifugal reactor 5 and the linear sliding rail 43 (specifically, the clamping jig 42) are on the same plane, and the linear track process can be converted into the circular motion track process through the design.
As shown in fig. 1 and 2, the wash liquid filling device 6 is a syringe-type or peristaltic pump-type automatic filling device located beside the wash liquid filling station of the linear slide 43, and includes a second wash liquid bottle 61, a pump 62, a conduit 63, a control valve 64, and a filling head 65. The second wash liquid bottle 61, pump 62 and fill head 65 are connected together by a conduit 63, and a control valve 64 is mounted on the conduit 63 between the pump 62 and fill head 65. In operation, the pump 62 is started to drive the washing liquid to push a designated volume of washing liquid to the washing liquid injection port of the joint inspection integrated reagent card 1 along the guide pipe 63 and the control valve 64 through the filling head 65 so as to meet the washing requirement of the joint inspection reaction tube 12.
As shown in fig. 1 to 3, the centrifugal washing device 7 is arranged beside the washing station of the linear slide rail 43 for through-type repeated washing of the joint inspection reaction tube 12 by centrifugal force. The structure of the centrifugal washing apparatus 7 is the same as that of the centrifugal reactor 5, and a description thereof will not be repeated here. The centrifugal washing device 7 rotates for a certain time according to the acceleration-deceleration-acceleration rhythm at a specified speed, the washing liquid in the washing liquid storage tank 13 of the joint inspection integrated reagent card 1 is driven by centrifugal force to be added into the joint inspection reaction tube 12 through the washing liquid diversion channel 141 and the liquid guide cavity 142, and the unbound material on the wall of the reaction tube is fully washed and discharged into the waste liquid storage tank 16, so that the washing operation is completed.
As shown in fig. 1, the fluorescence detection device 8 is disposed beside the fluorescence detection station of the linear slide rail 43 for performing fluorescence detection on the blood sample in the joint inspection reaction tube 12. The fluorescence detection means 8 may include an excitation light source, a fluorescence detection unit and a data analysis unit, a joint inspection integrated reagent card moving unit (not shown), and the like. The excitation light emitted by the excitation light source is projected to the detection surface of each joint inspection reaction tube 12 of the joint inspection integrated reagent card 1 according to a designed angle, the reaction products in the joint inspection reaction tubes 12 are excited to emit fluorescence, and the fluorescence detection unit and the data analysis unit detect the fluorescence intensity of the formed reactants in each variety of reaction tubes of the joint inspection integrated reagent according to a certain angle. The mechanical moving unit is used for moving the joint inspection integrated reagent 1 to scan and detect fluorescence one by one on each joint inspection reaction tube 12 on the joint inspection integrated reagent. The data analysis unit calculates concentration values of all items of the joint inspection integrated reagent or judges negative and positive according to the detected fluorescence intensity shown by a standard curve or a judging threshold value, and finally reports the result at the same time. Excitation light sources, fluorescence detection units and data analysis units are well known and will not be described further herein. Preferably, the detector of the fluorescence detection unit is a PMT or PD detector.
The working principle of the high-flux full-automatic microfluidic fluorescence immunoassay device is described in detail below.
And starting the instrument, pre-checking, and preheating to a normal working state.
The combined information of the sample pre-joint inspection project is set, and whether the set combined information is matched with a preset joint inspection integrated reagent in the instrument or not is judged and confirmed by the instrument.
According to the setting information, the turntable 2 rotates to rotate the joint inspection integrated reagent card 1 to be taken to a discharging position, and the mechanical arm 41 opens the joint inspection integrated reagent card 1, clamps and places the joint inspection integrated reagent card 1 on the sample injection station of the linear slide rail 43 to finish the operation of taking and loading the joint inspection integrated reagent card 1. The radio frequency specimen information collector 35 detects and identifies the labels of the specimen tubes on the specimen tube frame 34, confirms the corresponding specimens to be detected and the joint inspection integrated reagent cards 1 to be detected, decides the sampling sequence, volume and quantity of the whole blood automatic sampling device 3 and adds the blood samples into the joint inspection reaction tubes 12 of the joint inspection integrated reagent cards 1 of the sampling station. The joint inspection integrated reagent card transferring device 4 acts to transfer the joint inspection integrated reagent card 1 from the sample feeding station to the reaction station, namely to the reaction disc 52, and is fixed by the clamping device 54, the motor 51 drives the reaction disc 52 to rotate for a certain time according to a set rotating speed, and reactants in the joint inspection reaction tube 12 of the joint inspection integrated reagent card 1 are driven to flow, so that the reaction process is accelerated. The reaction disc rotation stopping device 53 clamps the side surface of the reaction disc 52 to prevent the rotation thereof; then, the joint inspection integrated reagent card transferring device 4 acts to transfer the joint inspection integrated reagent card 1 from the reaction station to the washing liquid filling station; next, the washing reagent filling device 6 performs disposable injection of a specified volume of washing reagent into the washing reagent injection port of the joint inspection integrated reagent card 1; then, the joint inspection integrated reagent card transferring device 4 acts to transfer the joint inspection integrated reagent card 1 from the washing liquid filling station to the washing station; the washing disc of the centrifugal washing device 7 rotates for a certain time according to the acceleration-deceleration-acceleration rhythm at a specified speed, washing liquid is driven into the joint inspection reaction tube 12 by centrifugal force, and the un-combined substances on the wall of the joint inspection reaction tube 12 are fully washed and discharged into the waste liquid storage tank 16, so that washing operation is completed; after the washing is finished, the joint inspection integrated reagent card transferring device 4 acts to transfer the joint inspection integrated reagent card 1 from the washing station to the fluorescence detection station, and fluorescence detection is finished through the fluorescence detection device 8 and a corresponding analysis report is given. The whole process is automatic, the working efficiency is high, and the detection of a plurality of items can be executed at one time.
While the invention has been particularly shown and described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (8)
1. A high-throughput fully-automatic microfluidic fluorescent immunoassay device, comprising:
The joint inspection integrated reagent card is provided with a plurality of parallel joint inspection reaction tubes;
The joint inspection integrated reagent card comprises an upper cover and a base which are connected integrally, wherein the upper cover and the base are combined together in a jogged mode and are provided with a washing liquid injection opening and a plurality of blood sample injection openings; the base is sequentially provided with a washing liquid storage tank, a plurality of sample loading liquid guide structures, a reaction tube mounting seat and a waste liquid storage tank along the flowing direction of the reagent; the washing liquid storage tank is communicated with the washing liquid injection port; the joint inspection reaction tube is fixedly inlaid in the reaction tube mounting seat and is provided with a slit-shaped inner cavity, two ends of the inner cavity are respectively provided with a liquid inlet and a liquid outlet, a characteristic marker membrane is arranged at the liquid inlet, and the liquid outlet is in fluid communication with the waste liquid storage tank; the sample loading liquid guide structure is positioned between the washing liquid storage tank and the reaction tube mounting seat; the sample loading liquid guide structures are independent, each sample loading liquid guide structure corresponds to one joint inspection reaction tube and one blood sample injection opening respectively, the sample loading liquid guide structures are communicated with the blood sample injection openings, one end of each sample loading liquid guide structure is communicated with the washing liquid storage tank, and the other end of each sample loading liquid guide structure is communicated with the joint inspection reaction tube;
The sample loading liquid guide structure comprises a washing liquid diversion channel and a liquid guide cavity, one end of the liquid guide cavity is in fluid communication with the washing liquid storage tank through the washing liquid diversion channel, and the other end of the liquid guide cavity is in communication with the liquid inlet;
The rotary table is provided with a plurality of storage tanks, and each storage tank is used for storing one joint inspection integrated reagent card;
The whole blood automatic sampling device is used for adding a whole blood sample to be detected into the joint inspection reaction tube;
The joint inspection integrated reagent card transferring device comprises a mechanical arm, a plurality of clamping jigs, a linear slide rail and a pushing device, wherein the clamping jigs are slidably arranged on each station of the linear slide rail and used for clamping the joint inspection integrated reagent card, the mechanical arm is used for transferring the joint inspection integrated reagent card from the turntable to a feeding station of the linear slide rail, and the pushing device is used for pushing and transferring the joint inspection integrated reagent card along each station in sequence;
The centrifugal reactor is arranged beside the reaction station of the linear slide rail and is used for carrying out centrifugal reaction on the blood sample in the joint inspection reaction tube;
The washing liquid can be led into the liquid guide cavity from the washing liquid diversion channel by virtue of centrifugal force and then enters the joint inspection reaction tube;
The washing liquid filling device is arranged beside a washing liquid filling station of the linear slide rail and is used for pushing and filling a specified volume of washing liquid into the joint inspection reaction tube;
The washing liquid filling device is arranged beside a washing station of the linear slide rail and is used for repeatedly washing the joint inspection reaction tube in a through mode through centrifugal force;
and the fluorescence detection device is arranged beside the fluorescence detection station of the linear slide rail and is used for carrying out fluorescence detection on the blood sample in the joint inspection reaction tube.
2. The high-throughput fully-automatic microfluidic fluoroimmunoassay device of claim 1, wherein the cross-section of said lumen is circular, semicircular, elliptical, rectangular or trapezoidal.
3. The high-throughput fully-automatic microfluidic fluorescence immunoassay device according to claim 1, wherein grooves are formed in four sides of the joint inspection integrated reagent card, and the grooves serve as clamping positions of the clamping jig.
4. The high-throughput full-automatic microfluidic fluorescence immunoassay device according to claim 1, wherein the full-blood automatic sampling device comprises a full-blood mixing device, a full-blood sample sampling device, a needle washing device, a sample pipe rack and a radio-frequency sample information collector, wherein the full-blood mixing device is used for clamping a test tube containing a full-blood sample to be detected from the sample pipe rack and carrying out rotary mixing so as to mix the full-blood sample to be detected, the full-blood sample sampling device is used for collecting a specified volume of the full-blood sample and adding the whole-blood sample into the joint inspection reaction tube, the needle washing device is used for washing a sampling needle of the full-blood sample sampling device, and the radio-frequency sample information collector is used for reading a serial number of the sample pipe and identifying the number and specific variety of items to be detected.
5. The high-throughput fully-automatic microfluidic fluoroimmunoassay device according to claim 1, wherein the plurality of clamping jigs are in driving connection with the first motor through a link mechanism to achieve simultaneous clamping and unclamping under the action of the first motor.
6. The high-throughput fully-automatic microfluidic fluoroimmunoassay device according to claim 5, wherein said propulsion device comprises a second motor and a third motor, said second motor for driving said clamping jig to reciprocate along said linear slide, and said third motor for driving said clamping jig to reciprocate transversely to said linear slide.
7. The high-throughput full-automatic microfluidic fluorescence immunoassay device according to claim 1, wherein the centrifugal reactor comprises a driving motor, a reaction disc and a reaction disc rotation stopping device, the driving motor is in driving connection with the reaction disc, a clamping device is arranged on the reaction disc, and the clamping device and the clamping jig are positioned on the same horizontal plane, so that the joint inspection integrated reagent card can be transferred between the clamping device and the clamping jig under the action of the propelling device, and the reaction disc rotation stopping device is used for preventing the reaction disc from rotating.
8. The high throughput fully automatic microfluidic fluoroimmunoassay device of claim 1, wherein said wash solution filling device comprises a wash solution bottle, a pump, a conduit, a control valve, and a filling head, said wash solution bottle, pump, and filling head being connected together by said conduit, said control valve being mounted on said conduit between said pump and said filling head.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010235482.4A CN113419073B (en) | 2020-03-30 | 2020-03-30 | High-flux full-automatic microfluidic fluorescence immunoassay device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010235482.4A CN113419073B (en) | 2020-03-30 | 2020-03-30 | High-flux full-automatic microfluidic fluorescence immunoassay device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113419073A CN113419073A (en) | 2021-09-21 |
| CN113419073B true CN113419073B (en) | 2024-05-31 |
Family
ID=77711637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010235482.4A Active CN113419073B (en) | 2020-03-30 | 2020-03-30 | High-flux full-automatic microfluidic fluorescence immunoassay device |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113419073B (en) |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010048631A2 (en) * | 2008-10-24 | 2010-04-29 | Biomicro, Inc. | Modular system for performing laboratory protocols and associated methods |
| CN105628947A (en) * | 2016-02-02 | 2016-06-01 | 徐恩良 | Whole blood autoluminescence immunoassay point-of-care test instrument |
| CN106680523A (en) * | 2017-03-09 | 2017-05-17 | 厦门先明生物技术有限公司 | Linear propulsion and parallel processing reaction device for integrated reagent group |
| WO2017128806A1 (en) * | 2016-01-27 | 2017-08-03 | 广州万孚生物技术股份有限公司 | Automatic fluorescence quantitative immunoassay analyzer and detection method |
| CN107121561A (en) * | 2016-02-24 | 2017-09-01 | 北京乐普医疗科技有限责任公司 | A kind of full-automatic fluorescence immunoassay quantitative analytical device |
| CN108704677A (en) * | 2018-04-27 | 2018-10-26 | 广州万孚生物技术股份有限公司 | A kind of micro-fluidic chip and the analytical instrument containing it |
| CN109444450A (en) * | 2018-12-27 | 2019-03-08 | 厦门先明生物技术有限公司 | A kind of whole blood sample automatic sampling apparatus |
| CN109490559A (en) * | 2018-11-19 | 2019-03-19 | 成都斯马特科技有限公司 | A kind of Full-automatic chemiluminescence immunoassay analysis meter |
| CN109759155A (en) * | 2019-03-14 | 2019-05-17 | 浙江扬清芯片技术有限公司 | A kind of multiple determination centrifugal type microfludic chip |
| CN109975563A (en) * | 2019-03-21 | 2019-07-05 | 厦门先明生物技术有限公司 | A kind of integrated reagent device of microfluid immunoassay |
| CN109975564A (en) * | 2019-03-21 | 2019-07-05 | 厦门先明生物技术有限公司 | A kind of integrated reagent automatic detection device of microfluid immunoassay |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101335726B1 (en) * | 2007-06-04 | 2013-12-04 | 삼성전자주식회사 | Disk type microfluidic device for conducting immunoassey and biochemistry analysis simultaneously |
-
2020
- 2020-03-30 CN CN202010235482.4A patent/CN113419073B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010048631A2 (en) * | 2008-10-24 | 2010-04-29 | Biomicro, Inc. | Modular system for performing laboratory protocols and associated methods |
| WO2017128806A1 (en) * | 2016-01-27 | 2017-08-03 | 广州万孚生物技术股份有限公司 | Automatic fluorescence quantitative immunoassay analyzer and detection method |
| CN105628947A (en) * | 2016-02-02 | 2016-06-01 | 徐恩良 | Whole blood autoluminescence immunoassay point-of-care test instrument |
| CN107121561A (en) * | 2016-02-24 | 2017-09-01 | 北京乐普医疗科技有限责任公司 | A kind of full-automatic fluorescence immunoassay quantitative analytical device |
| CN106680523A (en) * | 2017-03-09 | 2017-05-17 | 厦门先明生物技术有限公司 | Linear propulsion and parallel processing reaction device for integrated reagent group |
| CN108704677A (en) * | 2018-04-27 | 2018-10-26 | 广州万孚生物技术股份有限公司 | A kind of micro-fluidic chip and the analytical instrument containing it |
| CN109490559A (en) * | 2018-11-19 | 2019-03-19 | 成都斯马特科技有限公司 | A kind of Full-automatic chemiluminescence immunoassay analysis meter |
| CN109444450A (en) * | 2018-12-27 | 2019-03-08 | 厦门先明生物技术有限公司 | A kind of whole blood sample automatic sampling apparatus |
| CN109759155A (en) * | 2019-03-14 | 2019-05-17 | 浙江扬清芯片技术有限公司 | A kind of multiple determination centrifugal type microfludic chip |
| CN109975563A (en) * | 2019-03-21 | 2019-07-05 | 厦门先明生物技术有限公司 | A kind of integrated reagent device of microfluid immunoassay |
| CN109975564A (en) * | 2019-03-21 | 2019-07-05 | 厦门先明生物技术有限公司 | A kind of integrated reagent automatic detection device of microfluid immunoassay |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113419073A (en) | 2021-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3572815B1 (en) | Automatic analysis device and sample analysis method | |
| CA2392943C (en) | Chemistry system for a clinical analyzer | |
| CN110007099B (en) | Automatic analyzer and sample analyzing method | |
| CN107656085B (en) | Blood detector | |
| CN105628947B (en) | Whole blood automatic luminous immunoassay instant detector | |
| US6299839B1 (en) | System and methods for performing rotor assays | |
| CN107843583A (en) | A kind of micro-fluidic chemiluminescent analyzer and application method | |
| CN109975564B (en) | Automatic detection device for microfluid immunoassay integrated reagent | |
| CN207380068U (en) | A kind of micro-fluidic chemiluminescent analyzer | |
| CN113125787A (en) | Full-automatic chemiluminescence immunoassay analyzer | |
| CN114019178A (en) | Full-automatic immune biochemical integrated analyzer and use method thereof | |
| CN108414522B (en) | The all-in-one machine detected for micro-fluidic chip and NC film multi-pass amount | |
| CN201368879Y (en) | Biological test sensor | |
| US20210270819A1 (en) | Method and device for performing heterogeneous immunoassays | |
| CN113419073B (en) | High-flux full-automatic microfluidic fluorescence immunoassay device | |
| CN101504418B (en) | Bioassay sensor | |
| CN214310521U (en) | Turntable module | |
| CN215180272U (en) | Sample introduction module | |
| CN211697815U (en) | Full-automatic blood analyzer | |
| CN108008140B (en) | In-vitro diagnosis analysis system | |
| CN214794817U (en) | Detection card carrying module | |
| CN113009169B (en) | Automatic detector for multiple magnetosensitive biological chips | |
| CN214310527U (en) | Detection card transfer module | |
| CN217384867U (en) | Sampling arm module | |
| CN216696352U (en) | Full-automatic immune biochemical integrated analyzer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |