CN107843583B - Microfluidic chemiluminescence analyzer and application method thereof - Google Patents

Microfluidic chemiluminescence analyzer and application method thereof Download PDF

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CN107843583B
CN107843583B CN201710958630.3A CN201710958630A CN107843583B CN 107843583 B CN107843583 B CN 107843583B CN 201710958630 A CN201710958630 A CN 201710958630A CN 107843583 B CN107843583 B CN 107843583B
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chip
column
liquid
ultrasonic
module
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CN107843583A (en
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许行尚
杰弗瑞·陈
张前军
武亚
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Nanjing Lanyu Biological Technology Co Ltd
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Nanjing Lanyu Biological Technology Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76Chemiluminescence; Bioluminescence
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic 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

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Abstract

The invention relates to the technical field of microfluidics, in particular to a microfluidic chemiluminescence analyzer and a using method thereof. The invention integrates a plurality of devices, can scan codes for each chip and determine personalized detection items; the ultrasonic module is used for fully and uniformly mixing the sample, the reaction reagent and the luminescent substrate, and finally, optical detection is carried out, data is read, so that the whole detection procedure is standardized and automated, and the detection sensitivity is high and the result is reliable. On the basis of ensuring various detection functions, the invention has the advantages of greatly simplified structure, smaller volume, low manufacturing cost and simple and convenient operation, is suitable for the immediate detection at the patient side and can quickly obtain the detection result.

Description

Microfluidic chemiluminescence analyzer and application method thereof
Technical Field
The invention relates to the technical field of microfluidics, in particular to a microfluidic chemiluminescence analyzer and a using method thereof.
Background
Chemiluminescence immunoassay (C L IA) has the characteristics of high sensitivity, strong specificity, wide linear range, simple and convenient operation and the like, is widely applied to diagnosis of tumor markers, infectious diseases, endocrine functions, hormones and the like, has an increasing share in the Chemiluminescence market in recent years, gradually replaces enzyme-linked immunosorbent assay (E L ISA) to become the mainstream of immunodiagnosis, and detection contents include tumor markers, cardiac markers, thyroid energy, insulin, diabetes, infectious diseases, cytokines, hormones, anaphylactic reaction, concentration monitoring of therapeutic drugs and the like.
The Chinese chemiluminescence apparatus comprises a semi-automatic chemiluminescence apparatus, a full-automatic chemiluminescence apparatus and a portable chemiluminescence apparatus. The existing chemiluminescence detector is generally used for reading a 96-well or 48-well microporous plate, the sample adding time from the first hole to the last hole is longer, and the consistency and the accuracy of a detection result are influenced to a certain extent. When fewer samples are required for testing, the use of a single 96-well or 48-well microplate can be extremely wasteful.
The microfluidic chip technology integrates basic operation units of sample preparation, reaction, separation, detection and the like in biological, chemical and medical analysis processes into a micron-scale chip, and automatically completes the whole analysis process. Due to its great potential in the fields of biology, chemistry, medicine and the like, the method has been developed into a new research field crossing the disciplines of biology, chemistry, medicine, fluid, electronics, materials, machinery and the like. However, the documents combining chemiluminescence and microfluidic chips are rare, and the practical and industrial applicability is much less.
Chinese patent 200910154432.7 discloses a microfluidic chip for capillary electrophoresis separation and chemiluminescence detection, which has a single flow path structure, and has a low reaction efficiency due to insufficient mixing of the sample injection, and cannot achieve the maximum luminescence intensity. Some large-scale chemiluminescence equipment detection samples are large in quantity, samples are easy to confuse, and the instrument is complex in structure, large in size and high in manufacturing cost, and is not suitable for small hospitals and community clinics with small sample quantities. Some small devices only keep a simple mechanical control structure, and have great influence on the sensitivity and accuracy of sample detection.
In a word, the existing instrument has a complex structure and a large volume, is not suitable for the application of point-of-care testing (POCT), and has poor clinical detection convenience in practical application. The operation steps are complex, the steps of adding reagent, incubating, cleaning and the like need manual operation, human errors are easily caused, and the accuracy of the detection result is influenced. The detection consumes long time, and the working efficiency of the instrument is low.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides the microfluidic chemiluminescence analyzer which enables a microfluidic chip of the analyzer to be conveniently placed, accurately positioned, accurately and quickly detected, and has good repeatability and the using method thereof, and the invention combines the high sensitivity of the chemiluminescence technology and the high specificity of the immunology technology, and uses a bar code scanner to read the chip information and determine the personalized detection scheme during detection; the spring device ensures the integrity of the microfluidic chip and the tightness of the combination between the chip and the instrument; the liquid level detection column monitors the flow of the sample at any time, drives the valve stopping column to control the opening and closing of the valve device, and controls the detection reaction in a reaction area of the chip; the ultrasonic module can uniformly mix a sample, a reaction reagent, a luminescent substrate and the like in a chip reaction area; and finally, carrying out optical detection and reading data.
In order to achieve the purpose, the invention adopts the technical scheme that: the utility model provides a micro-fluidic chemiluminescence analysis appearance, includes liquid way gas circuit module, chip loading module, supersound module, and liquid way gas circuit module, chip loading module, supersound module set up its characterized in that in proper order: the chip loading module is used for placing a chip and driving the chip to move horizontally, and is provided with a chip clamping device; the liquid path and gas path module comprises a first power part, a gas blowing column, a cleaning liquid column, a bottom liquid column and a liquid level detection column, wherein the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are synchronously lifted under the control of the first power part; the liquid path and gas path module also comprises a second power part and a check valve column which is controlled by the second power part to lift; elastic mechanisms are arranged at the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column, the liquid level detection column and the check valve column; when the chip is positioned at the reaction position, the bottoms of the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are in flexible contact with the surface of the chip.
The gas blowing column, the cleaning liquid column and the base liquid column are all of hollow structures, the bottoms of the gas blowing column, the cleaning liquid column and the base liquid column are respectively provided with a gas blowing port, a cleaning liquid port and a base liquid port, and when the chip is located at the reaction position, the gas blowing port, the cleaning liquid port and the base liquid port are all in flexible contact with the surface of the chip.
The chip clamping device comprises a chip groove for placing a chip, and a heating sheet is arranged below the chip groove; the chip clamping device also comprises a chip clamping block positioned at the edge of the chip groove, a first elastic part positioned in the chip clamping block and a positioning block positioned outside the chip clamping block, and the end part of the positioning block is fixed; one end of the first elastic part is connected with the chip clamping block, and the other end of the first elastic part enters the hole of the positioning block and is connected with the positioning block.
The ultrasound transducer provides an ultrasound signal to the ultrasound module, which is prior art. The ultrasonic module comprises a third power part, an eccentric rod connected with the third power part, a connecting rod positioned at the end part of the eccentric rod and positioned at one end far away from the rotating shaft, an ultrasonic head fixing block fixed on the connecting rod, and an ultrasonic head extending upwards from the ultrasonic head fixing block, wherein the ultrasonic head is in flexible contact with the surface of the chip, and a third elastic part abutted against the lower end of the ultrasonic head is arranged in the ultrasonic head fixing block; the ultrasonic module also comprises an ultrasonic synchronous block fixedly connected with the ultrasonic head fixing block, the ultrasonic synchronous block is attached to the third linear guide rail, and the connecting rod is also fixedly connected with the ultrasonic synchronous block; the third power part enables the eccentric rod to rotate and drives the ultrasonic head fixing block, the ultrasonic synchronizing block and the connecting rod to synchronously rotate and lift, and the ultrasonic synchronizing block can move on the third linear guide rail.
The liquid path and gas path module comprises a liquid path and gas path fixing plate, the liquid path and gas path fixing plate is fixedly connected with the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column, the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are arranged in parallel in sequence, and the first power part pushes the liquid path and gas path fixing plate to lift; the elastic mechanism (namely a spring) is sleeved on the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column; when the liquid level detection column detects that the sample is about to enter the valve position inside the chip, the second power part pushes the valve stopping column to move downwards and presses the valve position of the chip.
The liquid path and gas path module is provided with a second linear guide rail, the second linear guide rail is fixed and the liquid path and gas path fixing plate moves on the second linear guide rail.
The chip loading module is also provided with a first linear guide rail, the gear rotates to drive the rack to move horizontally, the rack is attached to the surface of the first linear guide rail and moves synchronously with the first linear guide rail, and the end part of the rack is connected with the chip clamping device.
The analyzer is also provided with a counter, the counter is communicated with the PMT, the lower end of the PMT is used for aligning to the upper surface of the chip, and the chip is positioned between the light source and the PMT during optical detection.
The use method of the microfluidic chemiluminescence analyzer is characterized by comprising the following steps of:
(1) when the detection is started, the chip is placed into the chip loading device, and the chip is clamped and fixed by the chip clamping device; moving the chip loading device to enable the chip to enter the instrument;
(2) when the chip reaches the reaction position, the screw rod motor drives the liquid path gas path fixing plate to press downwards, the gas path liquid path module stops pressing when pressing the chip, and the upper parts of the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are all provided with independent spring devices, so that the gas blowing port, the cleaning liquid port, the bottom liquid port and the liquid level detection column are in flexible contact with the chip; when the liquid level detection column detects that the sample is about to enter the position of the valve inside the chip, the other screw rod motor of the gas circuit and liquid circuit module immediately drives the valve stopping column to press downwards to press the position of the valve on the chip, so that the sample does not move forwards continuously, and meanwhile, the air blowing pump stops working;
(3) the motor of the ultrasonic module rotates, an eccentric rod fixed on a motor shaft rotates, the eccentric rod drives a connecting rod to rotate, the connecting rod is connected with an ultrasonic head fixing block through a pin shaft, the end part of the connecting rod is also connected with an ultrasonic synchronizing block, the ultrasonic head fixing block is fixed on the ultrasonic synchronizing block, the ultrasonic synchronizing block is fixed on a linear guide rail, an ultrasonic head limiting groove is positioned in the ultrasonic head fixing block, and an ultrasonic head is limited in the ultrasonic head limiting groove and can slide up and down in the ultrasonic head limiting groove; when the motor rotates, the ultrasonic head is driven to move upwards, and the linear guide rail moves upwards simultaneously; when the ultrasonic head contacts the chip reaction area, the spring device below the ultrasonic head makes the ultrasonic head flexibly contact with the chip; after full contact, liquid in the reaction area is mixed uniformly by ultrasound, so that the sample and the reagent in the reaction area are reacted fully; after the ultrasonic mixing is finished, the ultrasonic module moves downwards and stops when reaching the initial position;
(4) cleaning liquid is injected into the cleaning pump, the cleaning liquid flows into a reaction area in the chip from a cleaning liquid port, and after cleaning for a plurality of times, a substrate pump is added with substrate liquid; the ultrasonic module moves upwards to mix uniformly, so that the substrate and the reagent react fully; after the reaction is finished, the chip loading device moves backwards to reach the optical detection module, data is read, the chip exits after the reading is finished, and the detection is finished.
In the step (2), after the chip reaches the fixed position, the bar code scanner reads the bar code on the chip, reads the information on the chip, determines whether the loading chip is matched with the input item, if not, an error prompt is reported, and if so, the next operation is carried out.
Compared with the prior art, the invention has the following advantages: the invention integrates a plurality of devices, can scan codes for each chip and determine personalized detection items; the ultrasonic module is used for fully and uniformly mixing the sample, the reaction reagent and the luminescent substrate, and finally, optical detection is carried out, and sample data is read, so that the whole detection procedure is standardized and automated, and the detection sensitivity is high and the result is reliable. On the basis of guaranteeing various detection functions, the structure of the device is greatly simplified, the size is small, the manufacturing cost is low, the operation is simple and convenient, the device is suitable for carrying out instant examination on the patient side, and the detection result can be quickly obtained.
Drawings
FIG. 1 is a front view of the complete machine of the present invention;
FIG. 2 is a perspective view of the present invention;
FIG. 3 is a schematic structural diagram of a chip loading module;
FIG. 4 is a schematic structural diagram of a chip clamping block and a chip slot in a chip loading module;
FIG. 5 is a schematic structural diagram of a liquid path and gas path module;
FIG. 6 is a schematic structural view of an ultrasound module;
FIG. 7 is a schematic diagram of a spring plunger of the liquid path/gas path module;
FIG. 8 is a schematic view of the structure of a gas blowing column, a cleaning liquid column, a bottom liquid column, and a liquid level detection column;
the ultrasonic detection device comprises a counter 1, a liquid path and gas path module 2, a chip loading module 3, an ultrasonic generator 4, an ultrasonic module 5, a cylinder at the upper part of 6a, a step end face of 6b, a cylinder at the lower part of 6c, a first screw rod motor 2a, a second screw rod motor 2b, a bar code scanner 2c, a second linear guide rail 2d, a spring 2e, a spring 2f, a first linear guide rail 3a, a rack 3b, a chip groove 3c, a chip clamping block 3d, a first elastic part 3e, a positioning block 3f, a heating plate 3g, an ultrasonic head 5a, an ultrasonic synchronizing block 5b, a third linear guide rail 5c, a fixed block 5d, an ultrasonic head limit groove 5e, a pin shaft 5f, a spring 5g, an air blowing port 7, a cleaning liquid port 8, a bottom liquid port 9, a liquid level detection column 10, a valve stop column 11, a flange bearing 12, a connecting rod 13, an eccentric rod 14 and a motor 15.
Detailed Description
The present invention will be further described with reference to the following examples.
According to the figures 1-8, a microfluidic chemiluminescence analyzer comprises a liquid path and gas path module 2, a chip loading module 3 and an ultrasonic module 5, wherein the liquid path and gas path module, the chip loading module and the ultrasonic module are sequentially arranged, the chip loading module is used for placing a chip and driving the chip to translate, and the chip loading module is provided with a chip clamping device; the liquid path and gas path module comprises a first power part (such as a first screw rod motor 2a), an air blowing port 7 (positioned at the bottom of an air blowing column), a cleaning liquid port 8 (positioned at the bottom of a cleaning liquid column), a bottom liquid port 9 (positioned at the bottom of the bottom liquid column) and a liquid level detection column 10, wherein the air blowing port 7 is synchronously lifted under the control of the first power part; the liquid path and gas path module also comprises a second power part (such as a second screw rod motor 2b) and a valve stopping column 11 which is controlled by the second power part to lift; elastic mechanisms (namely springs 2e) are arranged at the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column; the upper part of the check valve post is provided with an elastic mechanism (namely a spring plunger 2 f); when the chip is located the detection position, gas mouth, cleaning solution mouth, end liquid mouth, liquid level detection post all with chip upper surface flexible contact. The valve stopping column is formed by connecting the upper part of the valve stopping column (namely a spring plunger) and the lower part of the valve stopping column (also in a cylinder structure), and the top of the spring plunger and the nut of the second lead screw motor are fixed on the same fixing plate (the fixing plate is not a liquid path and gas path fixing plate).
According to fig. 8, the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are all composed of an upper column body 6a and a lower column body 6c, a spring (not shown in fig. 8) is sleeved on the upper column body, the diameter of the lower column body is larger than that of the upper column body, the joint surface of the upper column body and the lower column body is a step end surface 6b, the top end of the spring is propped against the lower surface of the liquid path gas path fixing plate, the bottom end of the spring is propped against the step end surface at the top of the lower column body, and the upper column body and. The liquid path and gas path fixing plate and the end surface of the step of the pillar have a limiting effect.
The chip clamping device comprises a chip groove 3c for placing a chip; the chip clamping device further comprises a chip clamping block 3d located at the edge of the chip groove, a first elastic part 3e and a positioning block 3f located outside the chip clamping block, the left end of the first elastic part is connected with the position on the right side in the chip clamping block, the right end of the first elastic part is placed in a left end hole of the positioning block and connected with the positioning block, and the right end of the positioning block is fixed (fig. 3 and 4). Before the chip is put into, chip clamp splice 3d left end has still covered a small amount of regions of chip groove 3c, and the chip is put into the back, and chip clamp splice 3d moves to the right, and chip clamp splice and chip contact area be the cambered surface (with the cambered surface structure phase-match of the corner of chip), because the existence of elastic component, the chip is pushed up by the chip clamp splice.
The chip loading module is also provided with a first linear guide rail 3a, the gear rotates to drive the rack to translate 3b, the rack is attached to the surface of the first linear guide rail and synchronously moves with the first linear guide rail, and the end part of the rack is connected with the chip clamping device.
The microfluidic chemiluminescence analyzer is also provided with a counter 1, the counter 1 is communicated with a Photomultiplier (PMT) and used for calculating the number of photons, the lower end of the photomultiplier (which is an optical detection module) is used for aligning with the upper surface of a chip, and a light source is arranged between the chip and the photomultiplier.
The ultrasonic module comprises a third power part (such as a motor 15), an eccentric rod 14 connected with a motor shaft of the third power part, a connecting rod 13 connected with the end part of the eccentric rod and positioned at one end far away from the motor shaft, an ultrasonic head fixing block 5d fixed on the connecting rod, and an ultrasonic head 5a extending upwards from the ultrasonic head fixing block, wherein the ultrasonic head is in flexible contact with a reaction area on the lower surface of the chip, and a third elastic part (namely a spring 5g) abutted against the lower end of the ultrasonic head is arranged in the ultrasonic head fixing block; the ultrasonic module further comprises an ultrasonic synchronizing block 5b fixedly connected with the ultrasonic head fixing block, the ultrasonic synchronizing block is attached to the third linear guide rail 5c, and the upper end of the connecting rod is also fixedly connected with the ultrasonic synchronizing block; the third power part enables the eccentric rod to rotate and drives the ultrasonic head fixing block, the ultrasonic synchronizing block and the connecting rod to synchronously rotate and lift, and the ultrasonic synchronizing block moves on the third linear guide rail (figure 6).
The liquid path and gas path module comprises a liquid path and gas path fixing plate, the liquid path and gas path fixing plate is fixedly connected with the air blowing port, the cleaning liquid port, the bottom liquid port and the liquid level detection column, the air blowing port, the cleaning liquid port, the bottom liquid port, the liquid level detection column and the check valve column are arranged in parallel in sequence, and the first power part pushes the liquid path and gas path fixing plate to lift; the elastic mechanism is sleeved on the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column; when the liquid level detection column detects that the sample is about to enter the position of the valve inside the chip, the second power part pushes the valve stopping column to move downwards and presses the position of the valve of the chip; the upper part of the valve stopping column is a spring plunger 2f (the spring plunger is an elastic structure and is a finished product); the liquid path and gas path module is provided with a second linear guide rail 2d which is fixed and the liquid path and gas path fixing plate moves on the second linear guide rail (fig. 5 and 7).
The specific detection process is as follows: when the detection is started, the synchronous motor drives the gear rack to move forwards and drives the chip loading device to move forwards, when the chip loading device moves out of the instrument, a chip is placed in the chip loading device, and the chip clamping device is arranged in the chip loading device and can fix the chip and enable the chip to be accurately positioned. The chip is put in place, and the synchronous motor drives the chip loading device to enter the instrument.
When the chip loading device reaches a fixed position (namely, a reaction position), the bar code scanner 2c above the chip reads the bar code on the chip, reads information on the chip, determines whether the loaded chip is matched with the input item, reports an error prompt if the loaded chip is not matched, and performs the next step operation if the loaded chip is matched with the input item. First lead screw motor drives liquid circuit gas circuit fixed plate and pushes down, stop pushing down when gas circuit liquid circuit device presses the chip, blow the mouth, the cleaning solution mouth, the end liquid mouth, there is independent spring assembly above every of liquid level detection post, guarantee to blow the mouth, the cleaning solution mouth, the end liquid mouth, liquid level detection post flexible contact chip, the chip can not destroyed, also can guarantee to blow the mouth simultaneously, the cleaning solution mouth, the end liquid mouth, the liquid level detection post can closely combine with the chip, can not take place to leak gas, the weeping problem. The pump of the gas blowing port starts to work first, the sample of the chip sample adding port is blown into the reaction area inside the chip, when the liquid level detection column detects that the sample is about to enter the position of the valve inside the chip, the other screw rod motor of the gas circuit liquid level device immediately drives the check valve column to press downwards, the valve device on the chip is pressed, the sample cannot continue to move forwards, and meanwhile, the gas blowing pump stops working.
The stepping motor of the ultrasonic module rotates, an eccentric rod fixed on a motor shaft rotates, a connecting rod mechanism is connected to an instrument through a pin shaft and the eccentric rod, a flange bearing 12 is arranged in the connecting rod and the pin shaft, the other end of the connecting rod is connected with an ultrasonic head fixing block 5d through the pin shaft 5f, the ultrasonic head fixing block is fixed on an ultrasonic synchronizing block 5b, the ultrasonic synchronizing block is fixed on a third linear guide rail 5c, an ultrasonic head limiting groove 5e is located in the ultrasonic head fixing block, and an ultrasonic head is limited in the ultrasonic head limiting groove and can slide up and down in the ultrasonic head limiting groove. When the synchronous motor rotates, the ultrasonic head is driven to move upwards through the mechanisms, the third linear guide rail moves upwards at the same time, the third linear guide rail controls the ultrasonic module to move linearly up and down, and the ultrasonic module is controlled not to shake left and right at the same time. When the ultrasonic head 5a contacts the chip reaction zone, the spring device (i.e. the spring 5g) under the ultrasonic head can make close contact with the chip, and simultaneously, the ultrasonic head can not crush the chip. And starting ultrasonic mixing to mix the liquid in the reaction area after full contact, so that the sample and the reagent in the reaction area are fully reacted. After the ultrasonic mixing is finished, the ultrasonic module moves downwards and stops when reaching the initial position.
At this time, the cleaning pump starts to inject cleaning liquid for cleaning, and after several times of cleaning, the substrate pump adds substrate liquid. The ultrasonic module moves upwards to mix evenly, so that the substrate and the reagent react fully. After the reaction is finished, the chip loading device moves backwards to reach the optical detection module to read data. And (4) after reading is finished, the chip is withdrawn, and detection is finished.
The chip loading device is provided with the chip clamping device, so that the chip can be fixed and accurately positioned. The micro-fluidic chip is provided with a bar code, a bar code scanner can read detection items of the chip so as to determine whether the detection items are matched with input items, and the instrument can add different amounts of cleaning solution and substrate solution according to the requirements of different detection items so as to detect different items in a personalized way. The gas blowing port, the cleaning liquid port, the bottom liquid port and the liquid level detection column are respectively provided with an independent spring device, so that the integrity of the chip and the tightness of combination between the chip and an instrument can be ensured. The liquid level detection column can monitor the flow of liquid in the chip, and when the sample reaches the valve position, the valve stopping column closes the valve to control the reaction to be carried out in the reaction area of the chip. The invention utilizes ultrasonic to uniformly mix the liquid in the reaction area for a plurality of times, so that the sample, the reagent, the cleaning solution, the substrate solution and the like can be uniformly mixed and fully reacted, and the accuracy of the detection result is ensured. And finally, the optical detection module detects the chip information, and a user can read data on the instrument.
The invention belongs to a small instrument, is easy to carry, simple and convenient to operate, reliable in detection result and good in sensitivity, reduces the operation steps of experimenters, and can avoid sample pollution and sample information confusion while improving the sample analysis efficiency. The incubation can be performed by a heat plate and all reactions are performed in a microfluidic chip without waste discharge. The microfluidic chemiluminescence analyzer can be applied to clinical detection and provides qualitative and quantitative basis for clinical treatment.
The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.

Claims (8)

1. The utility model provides a micro-fluidic chemiluminescence analysis appearance, includes liquid way gas circuit module, chip loading module, supersound module, and liquid way gas circuit module, chip loading module, supersound module set up its characterized in that in proper order: the chip loading module is used for placing a chip and driving the chip to move horizontally, and is provided with a chip clamping device; the liquid path and gas path module comprises a first power part, a gas blowing column, a cleaning liquid column, a bottom liquid column and a liquid level detection column, wherein the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are synchronously lifted under the control of the first power part; the liquid path and gas path module also comprises a second power part and a check valve column which is controlled by the second power part to lift; elastic mechanisms are arranged at the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column, the liquid level detection column and the check valve column; when the chip is positioned at the reaction position, the bottoms of the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are in flexible contact with the surface of the chip; the ultrasonic module comprises a third power part, an eccentric rod connected with the third power part, a connecting rod positioned at the end part of the eccentric rod and positioned at one end far away from the rotating shaft, an ultrasonic head fixing block fixed on the connecting rod, and an ultrasonic head extending upwards from the ultrasonic head fixing block, wherein a third elastic part abutted against the lower end of the ultrasonic head is arranged in the ultrasonic head fixing block; the gas blowing column, the cleaning liquid column and the bottom liquid column are all of hollow structures, the bottoms of the gas blowing column, the cleaning liquid column and the bottom liquid column are respectively provided with a gas blowing port, a cleaning liquid port and a bottom liquid port, and when the chip is positioned at the reaction position, the gas blowing port, the cleaning liquid port and the bottom liquid port are all in flexible contact with the surface of the chip; the ultrasonic module also comprises an ultrasonic synchronous block fixedly connected with the ultrasonic head fixing block, the ultrasonic synchronous block is attached to the third linear guide rail, and the connecting rod is also fixedly connected with the ultrasonic synchronous block; the third power part enables the eccentric rod to rotate and drives the ultrasonic head fixing block, the ultrasonic synchronizing block and the connecting rod to synchronously rotate and lift, and the ultrasonic synchronizing block can move on the third linear guide rail.
2. A microfluidic chemiluminescent analyzer according to claim 1 wherein: the chip clamping device comprises a chip groove for placing a chip; the chip clamping device also comprises a first elastic part, a chip clamping block positioned at the edge of the chip groove and a positioning block positioned outside the chip clamping block; one end of the first elastic part is connected with the chip clamping block, and the other end of the first elastic part is placed in the hole of the positioning block and connected with the positioning block.
3. A microfluidic chemiluminescent analyzer according to claim 1 wherein: the liquid path and gas path module comprises a liquid path and gas path fixing plate, the liquid path and gas path fixing plate is fixedly connected with the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column, the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are arranged in parallel in sequence, and the first power part pushes the liquid path and gas path fixing plate to lift; the elastic mechanism is sleeved on the upper parts of the air blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column; when the liquid level detection column detects that the sample is about to enter the valve position inside the chip, the second power part pushes the valve stopping column to move downwards and presses the valve position of the chip.
4. A microfluidic chemiluminescent analyzer according to claim 3 wherein: the liquid path and gas path module is provided with a second linear guide rail, the second linear guide rail is fixed and the liquid path and gas path fixing plate moves on the second linear guide rail.
5. A microfluidic chemiluminescent analyzer according to claim 1 wherein: the chip loading module is also provided with a first linear guide rail, the gear rotates to drive the rack to move horizontally, the rack is attached to the surface of the first linear guide rail and moves synchronously with the first linear guide rail, and the end part of the rack is connected with the chip clamping device.
6. A microfluidic chemiluminescent analyzer according to claim 1 wherein: the counter is communicated with the PMT, the lower end of the PMT is used for aligning to the upper surface of the chip, and when optical detection is carried out, the chip is positioned between the light source and the PMT.
7. The use method of the microfluidic chemiluminescence analyzer is characterized by comprising the following steps of:
(1) when the detection is started, the chip is placed into the chip loading device, and the chip is clamped and fixed by the chip clamping device; moving the chip loading device to enable the chip to enter the instrument;
(2) when the chip reaches the reaction position, the screw rod motor drives the liquid path gas path fixing plate to press downwards, the gas path liquid path module stops pressing when pressing the chip, and the upper parts of the gas blowing column, the cleaning liquid column, the bottom liquid column and the liquid level detection column are all provided with independent spring devices, so that the gas blowing port, the cleaning liquid port, the bottom liquid port and the liquid level detection column are in flexible contact with the chip; when the liquid level detection column detects that the sample is about to enter the position of the valve inside the chip, the other screw rod motor of the gas circuit and liquid circuit module immediately drives the valve stopping column to press downwards to press the position of the valve on the chip, so that the sample does not move forwards continuously, and meanwhile, the air blowing pump stops working;
(3) the motor of the ultrasonic module rotates, an eccentric rod fixed on a motor shaft rotates, the eccentric rod drives a connecting rod to rotate, the connecting rod is connected with an ultrasonic head fixing block through a pin shaft, the end part of the connecting rod is also connected with an ultrasonic synchronizing block, the ultrasonic head fixing block is fixed on the ultrasonic synchronizing block, the ultrasonic synchronizing block is fixed on a linear guide rail, an ultrasonic head limiting groove is positioned in the ultrasonic head fixing block, and an ultrasonic head is in the ultrasonic head limiting groove and can slide up and down; when the motor rotates, the ultrasonic head is driven to move upwards, and the linear guide rail moves upwards simultaneously; when the ultrasonic head contacts the chip reaction area, the spring device below the ultrasonic head makes the ultrasonic head flexibly contact with the chip; after full contact, liquid in the reaction area is mixed uniformly by ultrasound, so that the sample and the reagent in the reaction area are reacted fully; after the ultrasonic mixing is finished, the ultrasonic module moves downwards and stops when reaching the initial position;
(4) cleaning liquid is injected into the cleaning pump, the cleaning liquid flows into a reaction area in the chip from a cleaning liquid port, and after cleaning for a plurality of times, a substrate pump is added with substrate liquid; the ultrasonic module moves upwards to mix uniformly, so that the substrate and the reagent react fully; after the reaction is finished, the chip loading device moves backwards to reach the optical detection module, data is read, the chip exits after the reading is finished, and the detection is finished.
8. The use method of the microfluidic chemiluminescent analyzer of claim 7 wherein in step (2) when the chip reaches the reaction position, the barcode scanner reads the barcode on the chip, reads the information on the chip, determines whether the loaded chip matches the input item, if not, reports an error, and if so, proceeds to the next operation.
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