CN108760686B - Micro-fluidic chip for detecting turbidimetry and biochemical immunity machine using same - Google Patents
Micro-fluidic chip for detecting turbidimetry and biochemical immunity machine using same Download PDFInfo
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- CN108760686B CN108760686B CN201810889786.5A CN201810889786A CN108760686B CN 108760686 B CN108760686 B CN 108760686B CN 201810889786 A CN201810889786 A CN 201810889786A CN 108760686 B CN108760686 B CN 108760686B
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- 230000036039 immunity Effects 0.000 title claims abstract description 15
- 238000004879 turbidimetry Methods 0.000 title abstract description 16
- 239000003085 diluting agent Substances 0.000 claims abstract description 69
- 238000001514 detection method Methods 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 63
- 238000002156 mixing Methods 0.000 claims abstract description 33
- 238000004848 nephelometry Methods 0.000 claims abstract description 20
- 230000005540 biological transmission Effects 0.000 claims description 37
- 210000000078 claw Anatomy 0.000 claims description 19
- 239000011148 porous material Substances 0.000 claims description 8
- 230000007246 mechanism Effects 0.000 claims description 7
- 230000001174 ascending effect Effects 0.000 claims description 2
- 230000002146 bilateral effect Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 21
- 239000007788 liquid Substances 0.000 abstract description 19
- 238000004737 colorimetric analysis Methods 0.000 abstract description 9
- 230000035945 sensitivity Effects 0.000 abstract description 8
- 239000000523 sample Substances 0.000 description 73
- 239000000243 solution Substances 0.000 description 12
- 238000010586 diagram Methods 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 8
- 238000007865 diluting Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000007306 turnover Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- UVXCXZBZPFCAAJ-UHFFFAOYSA-N arc-111 Chemical compound C1=C2OCOC2=CC2=C(N(CCN(C)C)C(=O)C3=C4C=C(C(=C3)OC)OC)C4=CN=C21 UVXCXZBZPFCAAJ-UHFFFAOYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
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- 238000006116 polymerization reaction Methods 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/59—Transmissivity
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/19—Control of temperature characterised by the use of electric means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Automation & Control Theory (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The invention provides a micro-fluidic chip for detecting by a scattering turbidimetry method and a biochemical immunity machine using the chip, which belong to the field of detection equipment and comprise a body, a mixing tank and a reaction small hole, wherein the body is provided with a sample liquid adding tank, a sample quantitative tank and a sample overflow tank, the sample liquid adding tank is communicated with the sample quantitative tank, the sample quantitative tank is communicated with the sample overflow tank, the body is also provided with a diluent liquid adding tank, a diluent quantitative tank and a diluent overflow tank, the diluent liquid adding tank is communicated with the diluent quantitative tank, the diluent quantitative tank is communicated with the diluent overflow tank, the sample quantitative tank and the diluent quantitative tank are both communicated with the mixing tank, the mixing tank is communicated with the reaction small hole through a flow channel combination, one side of the reaction small hole, which is close to the center of the body, is a plane, and the corresponding position of the body and the outer ring of the reaction small hole is in an outwards convex arc shape. The invention effectively controls the divergence of light detected by the nephelometry, improves the sensitivity of the detected light intensity, and can be used for detection by a colorimetry and a nephelometry.
Description
Technical Field
The invention belongs to the field of detection equipment, relates to a biochemical and immune detection device, and particularly relates to a micro-fluidic chip for detecting turbidimetry by scattering and a biochemical immune machine using the chip.
Background
The micro-fluidic chip technology is a new technology for accurately manipulating and controlling nano-liter and pico-liter level fluid (biological sample fluid) in a micrometer-scale runner, and basic operation units such as sample preparation, reaction, separation, detection, cell culture, separation, cracking and the like related in the fields of chemistry, biology and the like can be integrated or basically integrated on a chip with a few square centimeters (even smaller), a network is formed by the micro-runner so as to control the fluid to penetrate through the whole system, and the micro-fluidic chip technology is used for replacing a technical platform with various functions of a conventional chemistry or biological laboratory.
Various methods for immune and biochemical detection exist, colorimetric methods are the main detection methods for biochemical detection, the detection principle is an analysis method established based on the selective absorption of light by a solution, the analysis method is also called a light absorption brightness method, the color of a colored substance solution is related to the concentration of the colored substance solution, and the concentration of the solution can be determined by utilizing optics to compare the depth of the color of the solution.
Turbidimetry is a main detection method of immunodetection, and is divided into a transmittance turbidimetry method and a scattering turbidimetry method, wherein the basic principle of the transmittance turbidimetry method is that an immune complex is formed after antigen and antibody are combined, and the complex is polymerized to generate turbidity within a certain time. When light passes through the solution, the light can be absorbed by the immune complex, the more the immune complex is, the light is absorbed in a certain range in proportion to the immune complex, and the detection principles of colorimetry and turbidimetry are shown in the figure 1; as shown in fig. 2, the basic detection principle of nephelometry is that when light with a certain wavelength irradiates along a horizontal axis, the light encounters antigen-antibody complex particles through a solution, the light is refracted by the particles and deflected, and the deflection angle of the light is closely related to the wavelength of emitted light and the size of the antigen-antibody complex particles. The intensity of scattered light is proportional to the content of the complex, i.e. the more antigens to be detected, the stronger the scattered light, in which method the monochromatic light source of the detection channel is arranged at an angle of typically 5 to 90 degrees to the photodetector.
At present, a biochemical detection chip based on a microfluidic technology is available in the market, various cuvettes of biochemical reaction are integrated into a reagent reaction hole in the periphery of a circular disc by using the microfluidic chip technology, so that biochemical detection items and immunity detection items detected by using a colorimetric method and a transmission nephelometry can be realized, but when the chip is used for detecting by using a scattering nephelometry, the reagent reaction hole of the chip is cylindrical, the inner wall of the detection hole and the outer wall of the chip form a structure similar to a plano-concave lens, the structure can have a divergent effect on scattered light, a part of light intensity is undetectable when the detector detects scattered light intensity, and the sensitivity of detecting the scattered light intensity with lower energy is insufficient, so that the performance index of the whole detection system can be influenced.
Disclosure of Invention
The invention aims to solve the problem of providing a micro-fluidic chip for detecting the nephelometry and a biochemical immunity machine using the micro-fluidic chip, so that the divergence of light detected by the nephelometry is effectively controlled, the sensitivity of the detected light intensity is improved, and the micro-fluidic chip can be used for detecting by a colorimetric method and a transmission nephelometry.
In order to solve the technical problems, the invention adopts the following technical scheme: the micro-fluidic chip for detecting by using the scattering nephelometry and the biochemical immunity machine using the micro-fluidic chip comprise a body, a mixing groove and a plurality of reaction small holes, wherein the mixing groove and the reaction small holes are arranged on the body, the mixing groove is communicated with the reaction small holes through a flow passage combination, one side of the reaction small holes, which is close to the center of the body, is a plane, and the position, which corresponds to one side, which is far away from the center of the body, of the reaction small holes is an arc which protrudes outwards.
Further, be equipped with sample adding liquid groove, sample ration groove and sample overflow launder on the body, sample adding liquid groove with sample ration groove passes through the microchannel intercommunication, sample ration groove's upper end with sample overflow launder intercommunication, still be equipped with diluent adding liquid groove, diluent ration groove and diluent overflow launder on the body, diluent adding liquid groove with diluent ration groove passes through the microchannel intercommunication, diluent ration groove's upper end with diluent overflow launder intercommunication, the mixing tank is established on the body and with sample adding liquid groove is in the homonymy, sample ration groove and diluent ration groove all pass through the microchannel with the mixing tank intercommunication.
Further, the flow channel combination comprises an annular flow channel and a plurality of radial flow channels, the annular flow channel is communicated with the mixing tank through a micro flow channel, the annular flow channel is coaxially arranged with the body, and each reaction small hole is communicated with the annular flow channel through one radial flow channel.
Further, the radial flow channel is perpendicular to the annular flow channel, and one side of the reaction small hole, which is far away from the outer ring of the body, is in an arc shape.
Further, the sample overflow groove and the diluent overflow groove are arranged on the same positioning circle with the reaction small holes, and the number of the diluent overflow grooves is larger than that of the sample overflow grooves.
Further, the number of the sample overflow grooves and the diluent overflow grooves is 1/4-1/5 of the number of the reaction small holes, and the sample overflow grooves and the diluent overflow grooves are adjacently arranged.
Furthermore, one side of each reaction pore is provided with an identification code, and the side surfaces of each sample overflow groove and each diluent overflow groove are also provided with identification codes.
Further, the position on the body corresponding to the reaction small hole is provided with an inward concave forming area, the forming area is U-shaped with an opening towards the outer ring of the body, the bottom surface of the forming area is provided with an outward convex condensation arc, and the radian of the condensation arc is larger than that of the outer ring circular part of the body in the forming area.
The biochemical immunity machine for detecting the microfluidic chip by using the scattering arm turbidity method comprises a left bracket, a right bracket, a centrifugal motor and a microfluidic chip, wherein the centrifugal motor is arranged between the left bracket and the right bracket and fixedly connected with the left bracket and the right bracket, the microfluidic chip is horizontally arranged and fixedly connected with an output shaft of the centrifugal motor, a transmission light source module and a scattering light source module are correspondingly arranged at the upper end of the edge of the microfluidic chip, the transmission light source module and the scattering light source module are arranged in a staggered manner, a transmission acquisition template is arranged at the lower end of the transmission light source module in a matched manner, a working end of the transmission acquisition module is arranged below the microfluidic chip, a scattering acquisition template is arranged at the lower end of the scattering light source module in a matched manner, and the scattering acquisition template is correspondingly arranged at the outer ring of the microfluidic chip.
Further, the transmission light source module and the scattering light source module are arranged in a staggered mode by 90 degrees, the transmission light source module is arranged on a lamp holder, the lamp holder is arranged between the left support and the right support, the transmission acquisition module is arranged between the left support and the right support and fixedly connected with the left support and the right support, and the scattering light source module and the scattering acquisition module are arranged on the right support.
Further, a temperature control upper plate and a temperature control lower plate are clamped between the left support and the right, the temperature control upper plate and the temperature control lower plate are horizontally arranged, the temperature control upper plate is arranged right above the micro-flow control, a first position avoiding hole is formed in the part, corresponding to the transmission light source module, of the temperature control upper plate, a second position avoiding hole is formed in the part, corresponding to the scattering light source module, of the temperature control upper plate, and the temperature control lower plate is arranged below the micro-flow control chip.
Furthermore, the microfluidic chip and the centrifugal motor are connected and separated through a locking device, and the locking device is of a mechanical clamping jaw structure.
Further, locking device includes locking claw, actuating arm, driving piece, fixed block and actuating lever, fixed block and centrifugal motor fixed connection, the driving piece is relative sliding connection about the fixed block, the lower extreme of driving piece with the actuating lever is connected, the actuating lever is gone up and down by cam mechanism drive, the bilateral symmetry of actuating piece upper end articulates the one end of actuating arm, the other end of actuating arm articulates the middle part of locking claw, the one end of locking claw articulates on the fixed block, the other end is kept away from the one end extension setting of fixed block, the symmetry setting locking claw is the ascending horn-shaped setting of opening.
Further, the cam mechanism comprises a plate cam and a lifting motor, the lifting motor is fixedly locked on the left bracket, the lifting motor drives the plate cam to rotate through a gear structure, the plate cam is vertically arranged, a roller is arranged at the lower end of the driving rod, and the roller is in contact with the outer ring of the plate cam.
Further, the microfluidic chip is arranged on the in-out bin frame, racks are arranged on two sides of the in-out bin frame, driving gears meshed with the racks are arranged on the two sides of the in-out bin frame, the driving gears are driven by an in-out motor to rotate, and the in-out motor is fixedly locked on the right support.
Further, the lower extreme of business turn over storehouse frame is equipped with the guide way, centrifugal motor passes through the motor cabinet and locks admittedly between left socle and the right branch frame, the upper end of motor cabinet is equipped with the guide post, the guide post is established in the guide way and both cooperation setting.
Compared with the prior art, the invention has the advantages and positive effects that: 1. the outer ring of the body is circular, one side of the reaction small hole, which is close to the outer ring of the body, is a plane, and the plane and the circular shape of the outer ring of the body form a planoconvex lens, so that more light rays are polymerized and received by the receiver, and the detection sensitivity is improved; 2. the sample overflow groove and the diluent overflow groove are adjacently arranged, so that the overflow condition of the sample and the diluent can be conveniently observed at the same position, the reaction small holes are intensively arranged, the concentrated detection in the detection process is convenient, the position searching is not needed, and the convenience of operation is improved; 3. after the identification codes are set, the body can identify and distinguish each reaction pore after rotating, meanwhile, the reaction pore, the sample overflow groove and the diluent overflow groove are conveniently distinguished, confusion is avoided after distinguishing, detection is carried out on the reaction pore, the scattered light intensity of the mixed liquid is judged, and when the sample overflow groove and the diluent overflow groove have overflow parts in practical application, the mixing can be carried out, so that the liquid in the sample quantitative groove and the diluent quantitative groove is in a full state; 5. the micro-fluidic chip is arranged on the centrifugal motor to realize centrifugation, quantification, dilution and mixing of sample-adding liquid, meanwhile, a transmission light source module and a scattering light source module are arranged at the edge of the micro-fluidic chip to work, and a transmission acquisition module and a scattering acquisition module are arranged to perform scattering and transmission detection simultaneously and perform transmission analysis of detection data, so that functions are integrated, one machine is multipurpose, resources are saved, the use cost of a user is saved, one sample single/multiple biochemical indexes and one single/multiple immune indexes can be detected at one time by combining the micro-fluidic chip, one sample multiple biochemical indexes and multiple immune indexes can be detected at one time, and the detection efficiency is greatly improved; 6. the temperature control upper plate and the temperature control lower plate are arranged, so that the temperature of the microfluidic chip can be controlled, and a plurality of sample adding liquids have certain requirements on the temperature, so that the temperature needs to be ensured in the detection process; 7. the microfluidic chip and the centrifugal motor are automatically separated and locked through the locking device, so that the placing efficiency in the detection process is improved, and meanwhile, the microfluidic chip is arranged on the bin inlet and outlet frame and can enter and exit along with the bin inlet and outlet frame, so that sample feeding is facilitated, and the operation convenience is improved.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention. In the drawings:
FIG. 1 is a schematic diagram of detection by colorimetry and turbidimetry;
FIG. 2 is a basic detection schematic of nephelometry;
FIG. 3 is a plan view of a micro-fluidic chip for detecting nephelometry and a biochemical immune machine using the micro-fluidic chip;
FIG. 4 is a schematic diagram of a local structure of an embodiment A of a micro-fluidic chip for detecting turbidimetry and a biochemical immunization machine using the same;
FIG. 5 is a graph showing the scattering of light during the actual inspection of FIG. 3 in accordance with the present invention;
FIG. 6 is a schematic diagram of a local structure of an embodiment B of a micro-fluidic chip for detecting turbidimetry and a biochemical immunization machine using the same;
FIG. 7 is a graph showing the scattering of light during the actual inspection of FIG. 5 in accordance with the present invention;
FIG. 8 is a schematic diagram of a biochemical immune machine for detecting a microfluidic chip by using a scattering arm turbidity method;
FIG. 9 is a schematic diagram of a biochemical immune machine for detecting a microfluidic chip by using a scattering arm turbidity method, which does not contain a right bracket, an in-out bin bracket and a transmission light source module;
FIG. 10 is a schematic diagram of the configuration of the centrifugal motor and motor mount of the present invention in combination;
FIG. 11 is a schematic diagram of the locking device of the present invention;
FIG. 12 is a schematic diagram of the light ray trend of scatter detection of the present invention;
FIG. 13 is a schematic diagram of the light ray trend of the transmission detection of the present invention;
FIG. 14 is a schematic diagram of a microfluidic chip of the present invention that performs scattering and transmission simultaneously.
Reference numerals:
1-a body; 11-a forming zone; 111-light-gathering arc; 2-sample addition tank; 21-a sample quantification trough; 22-sample overflow channel; 3-a diluent adding tank; 31-a diluent quantifying tank; 32-a diluent overflow tank; 4-a mixing tank; 5-reaction pores; 51-an identification code; 52-an annular flow channel; 53-radial flow path; a 6-receiver; 81-left bracket; 82-right rack; 83-microfluidic chip; 84-centrifuging the motor; 841-motor base; 842—a guide post; 85-a transmissive light source module; 851-lamp holders; 852-a transmission acquisition module; 86-a diffuse light source module; 861-scatter collection module; 87-a temperature control upper plate; 871-a first clearance hole; 872-a second clearance hole; 87' -temperature control lower plate; 88-entering and exiting the bin rack; 881-rack; 882-a drive gear; 883-in and out motor; 9-locking device; 91-a fixed block; 92-a drive block; 93-driving arm; 94-locking claws; 95-driving rod; 96-rollers; 97-plate cam; 98-lifting motor.
Detailed Description
It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other.
In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first", "a second", etc. may explicitly or implicitly include one or more such feature. In the description of the present invention, unless otherwise indicated, the meaning of "a plurality" is two or more.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be either fixedly connected, detachably connected, or integrally connected, for example; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art in a specific case.
Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
As shown in figure 3, the invention relates to a micro-fluidic chip for detecting turbidimetry and a biochemical immunity machine using the chip, which comprises a body 1, a mixing tank 4 and a reaction small hole 5, wherein the body 1 is provided with a sample adding tank 2, a sample quantifying tank 21 and a sample overflow tank 22, the sample adding tank 2 is communicated with the sample quantifying tank 21 through a micro-channel, the upper end of the sample quantifying tank 21 is communicated with the sample overflow tank 22, so as to ensure that samples flow among the sample adding tank 2, the sample quantifying tank 21 and the sample overflow tank 22 in sequence, the body 1 is also provided with a diluent adding tank 3, a diluent quantifying tank 31 and a diluent overflow tank 32, the diluent adding tank 3 is communicated with the diluent quantifying tank 31 through the micro-channel, the upper end of the diluent quantifying tank 31 is communicated with the diluent overflow tank 32, so as to ensure that diluent flows among the diluent adding tank 3, the diluent quantifying tank 31 and the diluent overflow tank 32 in sequence, the mixing tank 4 is arranged on the body 1 and is on the same side as the sample adding tank 2, the sample quantifying tank 21 and the diluent quantifying tank 31 are both communicated with the mixing tank 4 through micro-channels, the mixing tank 4 is communicated with the reaction small holes 5 through channel combination, the number of the reaction small holes 5 is a plurality of and are all arranged on the outer ring of the mixing tank 4, after the body 1 rotates, under the action of inertia, liquid in the mixing tank 4 passes through the channel combination flow channel reaction small holes 5, one side of the reaction small holes 5 close to the center of the body 1 is a plane, the corresponding positions of one side of the body 1, far away from the body 1, of the reaction small holes 5 are arc-shaped, and the plane and the circle of the outer ring of the body 1 form a planoconvex lens, so that more light rays are received by the receiver 6 in a polymerization manner, and the sensitivity of detection is improved; more preferably, the body 1 is circular.
Preferably, the flow channel combination comprises an annular flow channel 52 and a plurality of radial flow channels 53, the annular flow channel 52 is communicated with the mixing tank 4 through a micro-flow channel, the annular flow channel 52 is coaxially arranged with the body 1, each reaction small hole 5 is communicated with the annular flow channel 52 through one radial flow channel 53, the communication of a plurality of reaction small holes 5 and the mixing tank 4 is facilitated, and the structure can be symmetrically arranged, and is convenient to process and attractive; more preferably, the radial flow channel 53 is perpendicular to the annular flow channel 52, so that the liquid in the mixing tank 4 can enter the reaction small holes 5 more quickly after the body 1 rotates, one side of the reaction small holes 5 away from the outer ring of the body 1 is in an arc shape, the processing is convenient, and the scattering intensity can be improved.
Preferably, the sample overflow groove 22 and the diluent overflow groove 32 are arranged on the same positioning circle with the reaction small holes 5, so that the processing is convenient, the appearance is attractive, the number of the diluent overflow grooves 32 is larger than that of the sample overflow grooves 22, the overflow amount of the sample is smaller than that of the diluent, the device is arranged in a targeted manner, and the utilization rate of the device is improved.
Preferably, the number of the sample overflow grooves 22 and the diluent overflow grooves 32 and the number of the sample overflow grooves 22 and the diluent overflow grooves 32 which occupy 1/4-1/5 of the number of the reaction small holes 5 are adjacently arranged, so that the overflow conditions of the sample and the diluent can be conveniently observed at the same position, the reaction small holes 5 are intensively arranged, the concentrated detection in the detection process is convenient, the walking and the searching are not needed, and the convenience of operation is improved.
Preferably, one side of each reaction small hole 5 is provided with an identification code 51, the side surfaces of each sample overflow groove 22 and diluent overflow groove 32 are also provided with the identification code 51, after the identification code is set, the body 1 can also identify and distinguish each reaction small hole 5, and meanwhile, the reaction small holes 5, the sample overflow grooves 22 and the diluent overflow grooves 32 are conveniently distinguished, confusion is avoided after distinguishing, detection is carried out on the reaction small holes 5, the scattered light intensity of mixed liquid is judged, and in the practical application, the mixture can be carried out after the sample overflow grooves 22 and the diluent overflow grooves 32 have overflowed parts, so that the liquid in the sample quantitative groove 21 and the diluent quantitative groove 31 is guaranteed to be in a full state.
Example a: as shown in fig. 4 and 5, the inner wall of the reaction aperture 5 is a circular arc structure in which the side close to the center of the circle of the body 1 is kept, the side far from the center is made into a planar structure, and the edge of the outer ring of the body 1 is kept in a circular arc structure, so that the side of the reaction aperture 5 far from the center and the outermost ring of the body 1 form a plano-convex lens structure, and the structure not only can be used for reagent items for detection by colorimetry and turbidimetry, but also can avoid the problem of scattering of scattered light.
Example B: as shown in fig. 6 and 7, the inner wall of the reaction small hole 5 is a radian of a circular small hole kept at one side close to the center of the circle, one side far away from the center of the circle is made into a plane structure, a forming area 11 which is concave inwards is arranged at a position on the body 1 corresponding to the reaction small hole 5, the forming area 11 is U-shaped with an opening towards the outer ring of the body 1, a condensing arc 111 which is convex outwards is arranged on the bottom surface of the forming area 11, the radian of the condensing arc 111 is larger than that of the circular part of the outer ring of the body 1 of the forming area 11, the concentration degree of scattered light can be enhanced, the structure not only can be used for reagent items for detecting by a colorimetric method and a turbidimetric method, but also can realize the concentration effect of the scattered light, so that a detecting element receives more scattered light in a smaller space, and the sensitivity of a detecting system is improved.
The invention discloses a biochemical immunity machine for detecting a microfluidic chip by using a scattering arm turbidity method, as shown in fig. 8, 9 and 10, and relates to a biochemical and immunity integrated detection machine based on a microfluidic, which comprises a left bracket 81, a right bracket 82, a centrifugal motor 84 and a microfluidic chip 83, wherein the centrifugal motor 84 is arranged between the left bracket 81 and the right bracket 82 and fixedly connected with the left bracket and the right bracket, the microfluidic chip 83 is horizontally arranged and fixedly connected with an output shaft of the centrifugal motor 84, a transmission light source module 85 and a scattering light source module 86 are correspondingly arranged at the upper end of the edge of the microfluidic chip 83, the transmission light source module 85 and the scattering light source module 86 are arranged in a staggered manner, a transmission acquisition template is matched and arranged at the lower end of the transmission light source module 85, a scattering acquisition template is matched and arranged at the lower end of the scattering light source module 86, and the scattering acquisition template is correspondingly arranged with the outer ring of the microfluidic chip 83.
Preferably, the transmission light source module 85 and the scattering light source module 86 are arranged in a staggered mode by 90 degrees, the transmission light source module 85 is arranged on the lamp bracket 851, the lamp bracket 851 is arranged between the left bracket 81 and the right bracket 82, the transmission acquisition module 852 is arranged between the left bracket 81 and the right bracket 82 and fixedly connected with the left bracket and the right bracket, the scattering light source module 86 and the scattering acquisition module 861 are arranged on the right bracket 82, the staggered mode is arranged in a staggered mode by 90 degrees, and the structure is easy to lay out and more compact.
Preferably, a temperature control upper plate 87 and a temperature control lower plate 87 'are clamped between the left bracket 81 and the right, the temperature control upper plate 87 and the temperature control lower plate 87' are horizontally arranged, the temperature control upper plate 87 is just right above the micro-flow control, a first avoidance hole 871 is formed in a part of the temperature control upper plate 87 corresponding to the transmission light source module 85, a second avoidance hole 872 is formed in a part of the temperature control upper plate 87 corresponding to the scattering light source module 86, the temperature control lower plate 87 'is arranged below the micro-flow control chip 83, the temperature control upper plate 87 and the temperature control lower plate 87' are arranged, the temperature of the micro-flow control chip 83 can be controlled, a plurality of sample adding liquids have certain requirements on the temperature, therefore, the temperature needs to be ensured in the detection process, and more preferably, a temperature sensing switch is arranged on the left bracket 81 and used for sensing the temperature of the micro-flow control chip 83.
Preferably, the microfluidic chip 83 and the centrifugal motor 84 are connected and disconnected through the locking device 9, the locking device 9 is a mechanical clamping jaw structure, and the mechanical clamping jaw structure can adopt a pneumatic type, and the principle of the mechanical clamping jaw structure is the same as that of a pneumatic driving clamping jaw on a machine tool.
Preferably, as shown in fig. 11, the locking device 9 includes a locking claw 94, a driving arm 93, a driving block 92, a fixing block 91 and a driving rod 95, the fixing block 91 is fixedly connected with the centrifugal motor 84, the driving block 92 is vertically and slidably connected with the fixing block 91, the lower end of the driving block 92 is connected with the driving rod 95, the driving rod 95 is driven by a cam mechanism to vertically lift, two sides of the upper end of the driving block 92 are symmetrically hinged with one end of the driving arm 93, the other end of the driving arm 93 is hinged with the middle part of the locking claw 94, one end of the locking claw 94 is hinged on the fixing block 91, the other end of the locking claw 94 extends to one end far away from the fixing block 91, the symmetrically arranged locking claw 94 is arranged in a horn shape with an upward opening, the driving block 92 is driven to vertically move up and down, the driving arm 93 is further driven to open and close the locking claw 94, the locking claw 94 is arranged in a middle hole of the microfluidic chip 83, the locking claw 94 is closely attached to the microchip 83 in an open state, the locking claw 94 is driven to rotate together with the microfluidic chip 84, the centrifugal chip, the quantitative, the diluting and mixing actions are completed, when cleaning or sample adding products are required to be replaced after the detection is completed, the driving block 92 is driven to be separated from the driving block to drive the driving block to move to the driving arm 93 to be conveniently taken out from the microfluidic chip 84.
Preferably, the cam mechanism comprises a plate cam 97 and a lifting motor 98, the lifting motor 98 is fixedly locked on the left bracket 81, the lifting motor 98 drives the plate cam 97 to rotate through a gear structure, the plate cam 97 is vertically arranged, the lower end of a driving rod 95 is provided with a roller 96, the roller 96 is in contact with the outer ring of the plate cam 97, the plate cam 97 is driven by the lifting motor 98 to rotate, the roller 96 matched with the plate cam 97 is driven to lift up and down, the driving rod 95 is driven to lift up and down, and the mechanical transmission of the cam mechanism is adopted, so that the stability is high and the failure rate is low.
Preferably, the microfluidic chip 83 is arranged on the in-out bin frame 88, racks 881 are arranged on two sides of the in-out bin frame 88, a driving gear 882 is meshed with the racks 881, the driving gear 882 is driven by an in-out motor 883 to rotate, the in-out motor 883 is fixedly locked on the right bracket 82, the in-out motor 883 rotates, and the driving gear 882 is meshed with the racks 881, so that the movement of the in-out bin frame 88 is realized, and the taking and sample adding actions of the microfluidic chip 83 are facilitated; more preferably, the lower extreme of business turn over storehouse frame 88 is equipped with the guide way, and centrifugal motor 84 passes through motor cabinet 841 to be locked between left socle 81 and right branch frame 82, and the upper end of motor cabinet 841 is equipped with guide post 842, and guide post 842 is established in the guide way and both cooperate the setting, has guaranteed business turn over storehouse frame 88 accuracy and stability that removes after setting up guide post 842 and guide way, has realized the stability of micro-fluidic chip 83 operation.
In the practical application process, as shown in fig. 12, fig. 13 and fig. 14, after the equipment is started, firstly, the in-out motor 883 is started, the in-out frame 88 is moved out, then the microfluidic chip 83 is added into the microfluidic chip 83, then the in-out frame 88 is moved into the equipment, the microfluidic chip 83 reaches the appointed position of the equipment, the lifting motor 98 is started, the plate cam 97 realizes the lifting of the driving rod 95 through the roller 96, the locking claw 94 is stretched into a whole with the microfluidic chip 83, the microfluidic chip 83 rotates along with the centrifugal motor 84, the centrifugation, quantification, dilution, mixing and heating actions of the sample adding liquid are completed, then the equipment starts exposure detection, the turbidimetric scattering detection and transmission colorimetric detection are alternately performed, the transmission light source module 85 and the scattering light source module 86 work, the transmission acquisition module 852 and the scattering acquisition module 861 work, after the light data are collected, and the detection data are calculated and output the sample detection result through the built-in program, the built-in program for the detection is the known module on the market, the whole structure can be purchased for direct use, the whole structure is integrated and set up, the functions are realized, the functions of scattering and the whole structure can be integrated, the biochemical sample detection can be realized, one-time and multiple-used, multiple-level biochemical sample detection can be saved, multiple-level and multiple-level biochemical sample detection index can be realized, multiple-level and multiple-level detection index can be realized, and multiple-level detection index can be realized by using one or multiple-level biochemical sample detection index, and multiple-level can be more than the biochemical index, and multiple-level detection index can be detected by one by using
In the process of sample adding operation of the microfluidic chip, the method comprises the following steps of 1, adding a sufficient amount of sample to be detected in a sample adding groove, and metering a sufficient amount of diluent in a diluent adding groove; 2. the sample adding groove is communicated with the sample quantifying groove 21 through a micro-channel, the diluting sample adding groove is communicated with the diluting solution quantifying groove 31 through a micro-channel, the centrifugal motor 83 is started to drive the body 1 to rotate, the sample to be detected enters the sample quantifying groove 21 for quantification, the excessive sample enters the sample overflow groove 22, the diluting solution enters the diluting solution quantifying groove 31 for quantification, and the excessive diluting solution enters the diluting solution overflow groove 32; 3. the sample quantifying groove 21 is communicated with the mixing groove 4 through a micro-channel, the diluent quantifying groove 31 is communicated with the mixing groove 4 through a micro-channel, the quantified sample and the diluent enter the mixing groove 4 to be mixed according to a quantified proportion, and the proportion setting can be completed by setting the proportion of the diameter of the micro-channel for conveying the sample to the diameter of the micro-channel for conveying the diluent; 4. the reagent reaction small hole 5 is communicated with the mixing tank 4 through an annular flow channel 52 and a group of radial flow channels 53, and a sample to be tested diluted according to a certain proportion enters the reagent reaction small hole 5 for reaction; 5. after the light is received by the receiver 6, the concentration of the specific substance in the sample to be detected is detected by the transmitted and scattered light intensity of the detection reagent reaction small hole 5. When the detection is carried out by using a scattering turbidimetry, the sensitivity and the detection linear range of a detection system directly influenced by the intensity of scattered light are mainly aimed at the problem that a convex lens structure formed by a reaction pore 5 diverges scattered light intensity, so that part of the scattered light intensity cannot be detected by a detector, a planoconvex lens structure of a reagent reaction pore 5 is provided, the convex lens structure can realize the aggregation of the scattered light, a detection element can detect more light intensity in a smaller detection interval, and the structure not only can be used for reagent items for detection by a colorimetric method and a transmission turbidimetry, but also can effectively avoid the problem of scattering of the scattered light, and remarkably improves the sensitivity of the detection element for receiving the scattered light intensity.
The foregoing describes one embodiment of the present invention in detail, but the description is only a preferred embodiment of the present invention and should not be construed as limiting the scope of the invention. All equivalent changes and modifications within the scope of the present invention are intended to be covered by the present invention.
Claims (9)
1. The micro-fluidic chip for detecting by using a scattering nephelometry is characterized in that: the device comprises a body, a mixing tank and a plurality of reaction small holes, wherein the mixing tank and the reaction small holes are arranged on the body, the mixing tank is communicated with the reaction small holes through a runner combination, the inner wall of each reaction small hole is the radian of a circular small hole kept at one side close to the center of the body, one side far from the center of the circle is made into a planar structure, and the position, corresponding to one side of the body, far from the center of the body, of each reaction small hole is an arc which protrudes outwards;
The flow channel combination comprises an annular flow channel and a plurality of radial flow channels, the annular flow channel is communicated with the mixing tank through a micro flow channel, the annular flow channel is coaxially arranged with the body, each reaction small hole is communicated with the annular flow channel through one radial flow channel, the radial flow channels are perpendicular to the annular flow channels, and one side, away from the outer ring of the body, of each reaction small hole is in an arc shape.
2. The nephelometry detection microfluidic chip of claim 1, wherein: the device comprises a body, and is characterized in that a sample adding groove, a sample quantifying groove and a sample overflow groove are formed in the body, the sample adding groove is communicated with the sample quantifying groove through a micro-channel, the upper end of the sample quantifying groove is communicated with the sample overflow groove, a diluent adding groove, a diluent quantifying groove and a diluent overflow groove are further formed in the body, the diluent adding groove is communicated with the diluent quantifying groove through the micro-channel, the upper end of the diluent quantifying groove is communicated with the diluent overflow groove, and the mixing groove is formed in the body and is on the same side as the sample adding groove, and the sample quantifying groove and the diluent quantifying groove are communicated with the mixing groove through micro-channels.
3. The nephelometry detection microfluidic chip of claim 2, wherein: the sample overflow grooves and the diluent overflow grooves are arranged on the same positioning circle with the reaction small holes, the number of the diluent overflow grooves is larger than that of the sample overflow grooves, the sum of the sample overflow grooves and the diluent overflow grooves accounts for 1/4-1/5 of the number of the reaction small holes, and the sample overflow grooves and the diluent overflow grooves are adjacently arranged;
one side of each reaction pore is provided with an identification code, and the side surfaces of each sample overflow groove and each diluent overflow groove are also provided with identification codes.
4. The nephelometry detection microfluidic chip of claim 1, wherein: the device comprises a body, a reaction small hole, an inner concave forming area, an outer ring and a light condensing arc, wherein the position of the body corresponding to the reaction small hole is provided with the inwards concave forming area, the forming area is U-shaped with an opening towards the outer ring of the body, the bottom surface of the forming area is provided with the outwards convex light condensing arc, and the radian of the light condensing arc is larger than that of the outer ring circular part of the body in the forming area.
5. A biochemical immunity machine using the nephelometry detection microfluidic chip of claim 1, characterized in that: including left socle, right branch frame, centrifugal motor and micro-fluidic chip, centrifugal motor establishes in the middle of left socle and the right branch frame and with two fixed connection, micro-fluidic chip level set up and with centrifugal motor's output axle fixed connection, micro-fluidic chip marginal upper end corresponds and is equipped with transmission light source module and scattering light source module, transmission light source module and scattering light source module dislocation set, transmission light source module's lower extreme matching is provided with transmission acquisition template, transmission acquisition module's work end is established micro-fluidic chip's below, scattering light source module's lower extreme matching is provided with scattering acquisition template, scattering acquisition template with micro-fluidic chip's outer lane corresponds the setting.
6. The biochemical immunity apparatus for detecting micro-fluidic chip using nephelometry according to claim 5, wherein: the device is characterized in that a temperature control upper plate and a temperature control lower plate are clamped between the left support and the right, the temperature control upper plate and the temperature control lower plate are horizontally arranged, the temperature control upper plate is right arranged right above the micro-flow control, a first position avoiding hole is formed in the part, corresponding to the transmission light source module, of the temperature control upper plate, a second position avoiding hole is formed in the part, corresponding to the scattering light source module, of the temperature control upper plate, and the temperature control lower plate is arranged below the micro-flow control chip.
7. The biochemical immunity apparatus for detecting micro-fluidic chip using nephelometry according to claim 5, wherein: the micro-fluidic chip with centrifugal motor passes through locking device and realizes being connected and break away from, locking device includes locking claw, actuating arm, drive piece, fixed block and actuating lever, fixed block and centrifugal motor fixed connection, the drive piece is relative sliding connection about the fixed block, the lower extreme of drive piece with the actuating lever is connected, the actuating lever is gone up and down by cam mechanism drive, the bilateral symmetry of actuating block upper end articulates the one end of actuating arm, the other end of actuating arm articulates the middle part of locking claw, the one end of locking claw articulates on the fixed block, the other end is kept away from the one end of fixed block extends the setting, and the symmetry sets up the locking claw is the ascending horn-shaped setting of opening.
8. The biochemical immunity apparatus for detecting micro-fluidic chip using nephelometry according to claim 7, wherein: the cam mechanism comprises a plate cam and a lifting motor, wherein the lifting motor is fixedly locked on the left bracket, the lifting motor drives the plate cam to rotate through a gear structure, the plate cam is vertically arranged, a roller is arranged at the lower end of the driving rod, and the roller is in contact with the outer ring of the plate cam.
9. The biochemical immunity apparatus for detecting micro-fluidic chip using nephelometry according to claim 5, wherein: the micro-fluidic chip is arranged on the in-out bin frame, racks are arranged on two sides of the in-out bin frame and are meshed with the racks, driving gears are driven to rotate by an in-out motor, the in-out motor is fixedly locked on the right support, a guide groove is formed in the lower end of the in-out bin frame, the centrifugal motor is fixedly locked between the left support and the right support through a motor seat, a guide post is arranged at the upper end of the motor seat, and the guide post is arranged in the guide groove and is matched with the left support and the right support.
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| CN109847820A (en) * | 2019-04-18 | 2019-06-07 | 天津诺迈科技有限公司 | The pre-packaged device of micro-fluidic chip and application method |
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