CN110208522A - A kind of magnetic particle shines micro-fluidic chip and reaction method - Google Patents
A kind of magnetic particle shines micro-fluidic chip and reaction method Download PDFInfo
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- CN110208522A CN110208522A CN201910566930.6A CN201910566930A CN110208522A CN 110208522 A CN110208522 A CN 110208522A CN 201910566930 A CN201910566930 A CN 201910566930A CN 110208522 A CN110208522 A CN 110208522A
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/535—Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/54326—Magnetic particles
Abstract
The present invention is suitable for micro-fluidic chip electrochemiluminescent immunoassay detection technique field, a kind of luminous micro-fluidic chip of magnetic particle is provided, the chip includes: substrate, sample-adding portion, the homogeneous magnetic standard configuration body storage unit of liquid, the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand storage unit, solid-state tagged ligand, air pump, reaction zone, cleaning solution storage unit, cleaning solution and interconnecting piece；The homogeneous magnetic standard configuration body of liquid includes magnetic bead, temperature-sensitive material and solution.The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and the homogeneous magnetic standard configuration body storage unit of liquid of the storage homogeneous magnetic standard configuration body of liquid is set, separate the homogeneous magnetic standard configuration body of liquid when chip is not used with solid-state tagged ligand, three is sufficiently mixed with addition sample when detection, the speed of reaction can be effectively improved, to improve the sensitivity of detection, repeatability and accuracy.
Description
Technical field
The invention belongs to micro-fluidic chip electrochemiluminescent immunoassay detection technique field more particularly to a kind of magnetic particle shine it is micro-fluidic
Chip and reaction method.
Background technique
Currently, there are mainly two types of development trends for in-vitro diagnosis (IVD): one is automations, integrated integration, i.e., using big
Full-automatic, the highly sensitive large-scale instrument and equipment of matched central laboratory, type hospital realizes that high-precision diseases analysis is examined
Disconnected, the reagent of use is big packaging reagent, for multiple sample analysis；Another kind miniaturization, bed sideization immunity analysis instrument, adopt
With single packaged reagent, the quick analyzing and diagnosing in scene is realized.
Small hospital or community hospital's insufficient funds, sample size are few, are not appropriate for the large scale equipment of purchasing price valuableness, and
The sample for needing to analyze is few, and packs greatly after reagent is sealed off using limited time, leads to the expired waste of reagent.And what is minimized exempts from
Epidemic disease analyzer can solve small hospital or community hospital's large scale equipment be at high cost, reagent waste using single packaged reagent
The problem of.
Micro-fluidic chip is also known as chip lab (Lab-on-a-chip), refers to fields such as biology, chemistry and medicine
Involved in the basic operation units such as sample preparation, reaction, separation, detection be integrated into one piece with micro-meter scale microchannel
On chip, it is automatically performed the overall process of reaction and analysis.Based on micro-fluidic chip realize analysis and detection device the advantages of be: sample
This dosage is few, and analysis speed is fast, convenient for portable instrument is made, is highly suitable for instant, field assay.
But existing single packaged micro-fluidic chip reacts insufficient due to there is a problem of, so as to cause detection
When there is a problem of low sensitivity, poor repeatability, be disturbed it is obvious.
Summary of the invention
The embodiment of the present invention provides a kind of luminous micro-fluidic chip of magnetic particle, it is intended to solve existing micro-fluidic chip reaction not
Sufficiently, lead to low detection sensitivity, poor repeatability, be disturbed obvious problem.
The embodiments of the present invention are implemented as follows, provides a kind of luminous micro-fluidic chip of magnetic particle, and the chip includes:
Substrate；
Sample-adding portion being disposed on the substrate, being added for sample；
The homogeneous magnetic standard configuration body storage unit of the liquid being disposed on the substrate and it is stored in the liquid homogeneous magnetic standard configuration body storage
The homogeneous magnetic standard configuration body of liquid in portion；
Solid-state tagged ligand；
Air pump on the substrate is set；
The reaction zone for being disposed on the substrate, being connected to the sample-adding portion, the reaction zone is for sample and the homogeneous magnetic of liquid
Standard configuration body, solid-state tagged ligand, which generate, to be mixed and reacts；
Cleaning solution storage unit and the cleaning solution being stored in the cleaning solution storage unit；
The homogeneous magnetic standard configuration body of liquid includes magnetic bead, temperature-sensitive material and solution；
Between the reaction zone and the sample-adding portion, the reaction zone and the homogeneous magnetic standard configuration body storage unit of the liquid it
Between, between the reaction zone and the cleaning solution storage unit be provided with interconnecting piece；
The solid-state tagged ligand is arranged in the reaction zone, in the homogeneous magnetic standard configuration body storage unit of the liquid or institute
It states in the interconnecting piece between reaction zone and the homogeneous magnetic standard configuration body storage unit of the liquid.
Further, the solid-state tagged ligand includes the ligand of enzyme or luminous agent label；
The enzyme includes: one of horseradish peroxidase and alkaline phosphatase or a variety of；The luminous agent includes: acridine
One of ester, ABEI, fluorescent dye, fluorescin and fluorescent microsphere are a variety of.
Further, the chip further include:
The detection zone being connected to the reaction zone；
Luminescent solution storage unit and the luminescent solution being stored in luminescent solution storage unit；
Between the reaction zone and the detection zone, the company of being provided between the luminescent solution storage unit and the detection zone
Socket part.
Further, the sample-adding portion, the homogeneous magnetic standard configuration body storage unit of liquid, reaction zone, detection zone, cleaning solution storage
Micro- channel structure is used at portion, luminescent solution storage unit and each interconnecting piece at least one, it is micron that micro- channel is at least one-dimensional
Scale.
The embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, the solid-state tagged ligand
When being arranged in the reaction zone, which comprises
Sample is added from sample-adding portion and sample is made to enter reaction zone；
The homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit of liquid is put into reaction zone；
Sample is set to be sufficiently mixed, react in reaction zone with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand by air pump；
Compound after cleaning reaction.
The embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, the solid-state tagged ligand
Be arranged in the homogeneous magnetic standard configuration body storage unit of the liquid or the reaction zone and the homogeneous magnetic standard configuration body storage unit of the liquid it
Between interconnecting piece when, which comprises
Sample is added from sample-adding portion and sample is made to enter reaction zone；
It is put into after the homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit of liquid is mixed with solid-state tagged ligand
To reaction zone；
Sample is set to be sufficiently mixed, react in reaction zone with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand by air pump；
Compound after cleaning reaction.
The embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, and the reaction zone includes phase
Intercommunicated the first reaction subregion and the second reaction subregion, the solid-state tagged ligand is placed in the first reaction subregion, described
Method includes:
Sample is added from sample-adding portion and sample is made to enter the first reaction subregion；
The sample and solid-state tagged ligand is reacted in subregion first by air pump to be sufficiently mixed, react, marked
Remember ligand complex；
Tagged ligand compound is put into the second reaction subregion；
The homogeneous magnetic standard configuration body of liquid is put into the second reaction subregion, the tagged ligand compound and liquid are made by air pump
The homogeneous magnetic standard configuration body of state is sufficiently mixed in the second reaction subregion, reacts, and obtains resulting composite；
Resulting composite after cleaning reaction.
Further, the reaction zone is equipped with cleaning area；Compound after the cleaning reaction specifically includes:
Cleaning solution is put into the second reaction subregion, the resulting composite after cleaning reaction；Or
Resulting composite after reaction enters cleaning area, and cleaning solution is put into cleaning area, final after cleaning reaction
Compound.
The embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, and the reaction zone includes phase
Intercommunicated the first reaction subregion and the second reaction subregion, and the solid-state tagged ligand is placed in the second reaction subregion, institute
The method of stating includes:
Sample is added from sample-adding portion and sample is made to enter the first reaction subregion；
The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic mark of liquid are made by air pump
Ligand is sufficiently mixed in the first reaction subregion, reacts, and obtains magnetic standard configuration nanocrystal composition；
Magnetic standard configuration nanocrystal composition is put into the second reaction subregion；
The magnetic standard configuration nanocrystal composition is reacted in subregion second with solid-state tagged ligand by air pump to be sufficiently mixed, instead
It answers, obtains resulting composite；
Resulting composite after cleaning reaction.
The embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, and the reaction zone includes phase
Intercommunicated the first reaction subregion and the second reaction subregion, and the first reaction subregion is connected to the sample-adding portion, solid-state label is matched
Body is placed on the second reaction subregion, which comprises
Sample is added from sample-adding portion and sample is made to enter the first reaction subregion；
The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic mark of liquid are made by air pump
Ligand is sufficiently mixed in the first reaction subregion, reacts, and obtains magnetic standard configuration nanocrystal composition；
Magnetic standard configuration nanocrystal composition after cleaning reaction；
Magnetic standard configuration nanocrystal composition after cleaning is put into the second reaction subregion；
The magnetic standard configuration nanocrystal composition is reacted in subregion second with solid-state tagged ligand by air pump to be sufficiently mixed, instead
It answers, obtains resulting composite.
The beneficial effects obtained by the present invention are as follows the embodiment of the present invention is marked by using the homogeneous magnetic standard configuration body of liquid and solid-state
Ligand, and be arranged storage the homogeneous magnetic standard configuration body of liquid the homogeneous magnetic standard configuration body storage unit of liquid, make the homogeneous magnetic standard configuration body of liquid with
The separation when chip is not used of solid-state tagged ligand, when detection with sample be added be sufficiently mixed three, can effectively mention
The speed of height reaction, to improve the sensitivity of detection, repeatability and accuracy.
Detailed description of the invention
Fig. 1 is the detonation configuration figure of the luminous micro-fluidic chip one embodiment of magnetic particle provided in an embodiment of the present invention；
Fig. 2 is the flow chart of the reaction method for the luminous micro-fluidic chip of magnetic particle that the embodiment of the present invention seven provides；
Fig. 3 is the flow chart of the reaction method for the luminous micro-fluidic chip of magnetic particle that the embodiment of the present invention eight provides；
Fig. 4 is the detonation configuration figure of luminous another embodiment of micro-fluidic chip of magnetic particle provided in an embodiment of the present invention；
Fig. 5 is the flow chart of the reaction method for the luminous micro-fluidic chip of magnetic particle that the embodiment of the present invention nine provides；
Fig. 6 is the flow chart of the reaction method for the luminous micro-fluidic chip of magnetic particle that the embodiment of the present invention ten provides；
Fig. 7 is the flow chart of the reaction method for the luminous micro-fluidic chip of magnetic particle that the embodiment of the present invention 11 provides.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
The present invention mixes sample, reacts, separating and detection is integrated on chip by using microfluidic chip technology,
And all reagent components needed for reaction are integrated on chip；It is easy to operate, when detection, sample only need to be added, close the lid,
Chip is put into miniature portable necessary instrument.
Embodiment one
As shown in Figure 1, the embodiments of the present invention are implemented as follows, a kind of luminous micro-fluidic chip of magnetic particle, institute are provided
Stating chip includes:
Substrate；
Sample-adding portion 21 being disposed on the substrate, being added for sample；
It the homogeneous magnetic standard configuration body storage unit 23 of the liquid being disposed on the substrate and is stored in the homogeneous magnetic standard configuration body of the liquid and deposits
The homogeneous magnetic standard configuration body of liquid in storage portion 23；
Solid-state tagged ligand；
Air pump 22 on the substrate is set；
The reaction zone 24 for being disposed on the substrate, being connected to the sample-adding portion 21, the reaction zone are equal with liquid for sample
Phase magnetic standard configuration body, solid-state tagged ligand, which generate, to be mixed and reacts；
Cleaning solution storage unit 25 and the cleaning solution being stored in the cleaning solution storage unit 25；
The homogeneous magnetic standard configuration body of liquid includes magnetic bead, temperature-sensitive material and solution；
Between the reaction zone and the sample-adding portion 21, the reaction zone and the homogeneous magnetic standard configuration body storage unit 23 of the liquid
Between, between the reaction zone and the cleaning solution storage unit 25 be provided with interconnecting piece 27；
The solid-state tagged ligand is arranged in the reaction zone 24, in the homogeneous magnetic standard configuration body storage unit 23 of the liquid,
Or in the interconnecting piece 27 between the reaction zone and the homogeneous magnetic standard configuration body storage unit 23 of the liquid.
Wherein, magnetic bead includes carboxyl magnetic bead, amino magnetic bead, Streptavidin MagneSphere, antibody modification magnetic bead and Modified antigen
One of magnetic bead is a variety of；Temperature-sensitive material is heat-convertible gel, includes gelatin, agar, alginate, carragheen, hydroxyl
One of methylcellulose, Arabic gum, guar gum, the ashamed bean gum of thorn, pectin, starch and xanthan gum are a variety of；Solution is packet
The buffer system of surfactant, protein is contained.
The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and it is homogeneous that storage liquid is arranged
The homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand is not used in chip in the homogeneous magnetic standard configuration body storage unit of the liquid of magnetic standard configuration body
When separate, when detection, since the homogeneous magnetic standard configuration liquid flowability of liquid liquid is good, match the homogeneous magnetic standard configuration body of liquid, solid-state label
Body is sufficiently mixed three with sample is added, and can effectively improve the speed of reaction, to improve the sensitivity of detection, again
Renaturation and accuracy.
Specifically, the cleaning solution removes analyte, the luminous agent marker of non-specific adsorption for cleaning magnetic bead
And the substance of other influences testing result.Cleaning solution mainly includes buffer system, protein and surfactant, wherein buffer body
System is 6.0~10.0 including but not limited to borate, phosphate, Tris-HCl and acetate etc., the pH range of cleaning solution.Wherein
Protein is including but not limited to bovine serum albumin(BSA), casein etc..Wherein surface-active including but not limited to may include polysorbas20,
Tween 80, triton x-100, polyethylene glycol and polyvinylpyrrolidone etc..Preferably, using cleaning in the present embodiment
Liquid is the pH7.0Tris-HCl buffer comprising bovine serum albumin(BSA), tween 20 and Proclin300.
Specifically, the homogeneous magnetic standard configuration body storage unit 23 of the liquid and cleaning solution storage unit 25 are seal chamber, sealing used
Material uses elastic material or high-isolation film, specially glass, plastics, rubber, aluminium foil or high-isolation film, wherein sealing material
Material can form for same material, can also be composed for multiple material.Under physical impact, storage unit can partial fracture, thus
The material of storage is released.
Air pump 22 is the air bag being built on the top plate 11 of substrate, which is connected to interconnecting piece 27, by repeatedly extruding
Or release air bag, so that the air in air bag is passed in and out interconnecting piece 27 repeatedly.The air pump 22 is used to absorb or be press-connected the sky in portion 27
Gas makes the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand and sample flow to reaction zone 24, and passes through absorption repeatedly or the company of extruding
The air of socket part 27 is sufficiently mixed the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand and sample in reaction zone 24.But
22 need of work of air pump is realized in sealed environment, and in order to seal chip interior, 134 are also set at the adding mouth in sample-adding portion 21
It is equipped with sealing cover 133, after sample is added in sample-adding portion 21, then covers sealing cover 133.
Specifically, the homogeneous magnetic standard configuration body of liquid is the mixed uniformly marked by magnetic bead ligand of liquid.
Embodiment two
On the basis of example 1, the solid-state tagged ligand includes the ligand of luminous agent label.
The luminous agent can also include: one of acridinium ester, ABEI, fluorescent dye, fluorescin and fluorescent microsphere
Or it is a variety of.
The cleaning solution storage unit 25 and the cleaning solution being stored in cleaning solution storage unit 25；
The detection zone 28 being connected to the cleaning area 29；
Luminescent solution storage unit 26 and the luminescent solution being stored in luminescent solution storage unit 26, for further cleaning magnetic bead or increasing
Strong luminous signal；
Between the cleaning area 29 and the detection zone 28, between the luminescent solution storage unit 26 and the detection zone 28
It is provided with interconnecting piece 27.
Specifically, the ligand includes: one of antigen, antibody, haptens and nucleic acid or a variety of.
Luminous agent is in conjunction with analyte or competes, and forms luminous agent tagged ligand；Magnetic particle marker in conjunction with analyte or
Competition, forms marked by magnetic bead ligand, both described ligands may be the same or different；The magnetic marker ligand, luminous agent label are matched
The ligand that body uses include nucleic acid, antigen, monoclonal antibody, polyclonal antibody and hormone receptor, the analyte include DNA,
Small molecule (drug or drugs), antigen, antibody, hormone, antibiotic, bacterium or virus and other biochemical markers.
In the present embodiment, the solid-state tagged ligand can with the homogeneous magnetic mark ligand binding (such as double antibody sandwich method) of liquid or
Person and tagged ligand competition (such as competition law).Wherein the ligand of luminous agent label can be identical as the homogeneous magnetic standard configuration body of liquid,
It can be different.Preferably, in one embodiment of the invention, selecting two kinds of different antibodies as solid-state tagged ligand and liquid
The homogeneous magnetic standard configuration body of state tests and analyzes object with double antibody sandwich method.
Embodiment three
On the basis of example 1, the solid-state tagged ligand includes the ligand of enzyme label；
The enzyme includes: one of horseradish peroxidase and alkaline phosphatase or a variety of.The ligand include: antigen,
One of antibody, haptens and nucleic acid are a variety of.
Enzyme is in conjunction with analyte or competes, and forms enzyme tagged ligand；Magnetic particle marker is in conjunction with analyte or competes, and is formed
Marked by magnetic bead ligand, both described ligands may be the same or different；The ligand that the magnetic enzyme tagged ligand, enzyme tagged ligand use
Comprising nucleic acid, antigen, monoclonal antibody, polyclonal antibody and hormone receptor, the analyte include DNA, small molecule (drug or
Drugs), antigen, antibody, hormone, antibiotic, bacterium or virus and other biochemical markers.
In the present embodiment, the solid-state tagged ligand can with the homogeneous magnetic mark ligand binding (such as double antibody sandwich method) of liquid or
Person and the homogeneous magnetic mark Ligand Competition (such as competition law) of liquid.Wherein the ligand of enzyme label can be with the homogeneous magnetic standard configuration body phase of liquid
Together, it can also be different.Preferably, in one embodiment of the invention, two kinds of different antibodies is selected to match as solid-state label
Body and the homogeneous magnetic standard configuration body of liquid are with double antibody sandwich method detection and analysis object.In another embodiment of the invention, one kind is selected
Antigen and a kind of antibody detect sample respectively as solid-state tagged ligand and the homogeneous magnetic standard configuration body of liquid with competition law.
Example IV
On the basis of embodiment two or three, the chip further include:
The detection zone 28 being connected to the reaction zone；
Luminescent solution storage unit 26 and the luminescent solution being stored in luminescent solution storage unit 26；
It is all provided between the reaction zone and the detection zone 28, between the luminescent solution storage unit 26 and the detection zone 28
It is equipped with interconnecting piece 27.
Specifically, the reaction zone is equipped with cleaning area, the detection zone 28 is connected to the cleaning area.
It in the present embodiment, carries out chemiluminescence and needs luminescent solution, and light emitting source is then also needed using fluorescence radiation.
Detection zone 28 is set, convenient for resulting composite being moved to detection zone 28 and is seen after cleaning solution being cleaned
It examines and detects, be easy to use, it is simple and convenient.
Specifically, the substrate is additionally provided with the waste liquid storage unit 30 being connected to the cleaning area 29.Convenient for collect cleaning and
Waste liquid after reaction can reduce interference of the waste liquid to detection, effectively improve the precision of detection.
Embodiment five
On the basis of example IV, the sample-adding portion 21, the homogeneous magnetic standard configuration body storage unit 23 of liquid, solid-state tagged ligand
Storage unit, reaction zone 24, detection zone 28, cleaning solution storage unit 25, luminescent solution storage unit 26 and each interconnecting piece 27 at least one
Place uses micro- channel structure, and it is micro-meter scale that micro- channel is at least one-dimensional.
Micro-fluidic chip of the invention will test all reagent component (the homogeneous magnetic standard configuration bodies of liquid, solid-state needed for process
Tagged ligand, cleaning solution, luminescent solution etc.) it integrates, be built into micro-fluidic chip, and by ingenious micro- channel design, matching
Under the operation for covering instrument, realize that the operating in a key of micro-fluidic chip (only need to be can be achieved with detecting, without complicated behaviour by start button
Make), whole blood separation, immune response, cleaning separation, chemiluminescence detection are realized, so as to avoid tying in existing micro-fluidic chip
Structure design is simple, detection when it is complicated for operation the deficiencies of and defect.Serum or blood can only be carried out by also overcoming traditional chemical light-emitting appearance
The shortcomings that starching detection, and whole blood sample cannot being detected.
Embodiment six
On the basis of example 1, the substrate includes:
Top plate 11；
The top adhesive tape 13 at 11 top of top plate is set；
The bottom tape 14 of 11 bottom of top plate is set；
The sample-adding portion 21, the homogeneous magnetic standard configuration body storage unit 23 of liquid, reaction zone 24 and each interconnecting piece 27 are arranged at institute
It states on top plate 11.
In the present embodiment, the moulding material of the substrate is polymer, including but not limited to polystyrene, polyvinyl chloride,
Polypropylene, epoxy resin etc..
The embodiment of the present invention uses microfluidic chip technology, and sample is mixed, is reacted, is separated and detection is integrated in chip
On, and all reagent components needed for reaction are integrated on chip.It is easy to operate, when detection, sample only need to be added, close the lid
Son is put into chip in miniature portable necessary instrument.
The top adhesive tape 13 be equipped be used cooperatively with the homogeneous magnetic standard configuration body storage unit 23 of liquid first window 131, with
It both cleaning solution storage unit 25, luminescent solution storage units 26 the second windows 132 being used cooperatively and is used cooperatively with sample-adding portion 21
Adding mouth 134 is equipped with sealing cover 133 at the adding mouth 134.First window 131 and the second window 132 are set, convenient for passing through
Pressure ram puts in chip interior out of first window 131 and the second window 132 and squeezes each storage unit, so that in each storage unit
Liquid substance outflow；And sealing cover 133 is set, convenient for sealing sample-adding portion 21, so that chip interior keeps sealing, just
It works in air pump.
In an alternate embodiment of the present invention where, the substrate includes: top plate and bottom plate, the top plate and the bottom plate
On be provided with the sample-adding portion 21, the homogeneous magnetic standard configuration body storage unit 23 of liquid, reaction zone 24 and each interconnecting piece 27.
Embodiment seven
As shown in Fig. 2, the embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, solid-state mark
When remembering that ligand is arranged in the reaction zone, which comprises
Sample is added from sample-adding portion 21 and sample is made to enter reaction zone；
The homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit 23 of liquid is put into reaction zone；
Sample and the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand are sufficiently mixed in reaction zone, instead by air pump 22
It answers；
Compound after cleaning reaction.
Specifically, the reaction zone is equipped with cleaning area, and the compound after the cleaning reaction specifically includes:
Cleaning solution is put into reaction zone, the compound after cleaning reaction；Or
So that the compound after reaction is entered cleaning area by air pump 22, and cleaning solution is put into cleaning area, cleaning reaction
Compound afterwards.
The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and it is homogeneous that storage liquid is arranged
The homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand is not used in chip in the homogeneous magnetic standard configuration body storage unit of the liquid of magnetic standard configuration body
When separate, when detection with sample be added be sufficiently mixed three, the speed of reaction can be effectively improved, to improve detection
Sensitivity, repeatability and accuracy.In addition, sample is mixed with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand in reaction zone,
Single step reaction improves detection efficiency, and cleans magnetic bead by cleaning solution, removes analyte, the luminous agent mark of non-specific adsorption
The substance for remembering object and other influences testing result, can further increase the precision of detection.
Embodiment eight
As shown in figure 3, the embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, solid-state mark
Remember that ligand is arranged in the homogeneous magnetic standard configuration body storage unit 23 of the liquid or the reaction zone and the homogeneous magnetic standard configuration body of the liquid
When interconnecting piece 27 between storage unit 23, which comprises
Sample is added from sample-adding portion 21 and sample is made to enter reaction zone；
It is put after the homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit 23 of liquid is mixed with solid-state tagged ligand
Enter to reaction zone；
Sample and the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand are sufficiently mixed in reaction zone, instead by air pump 22
It answers；
Compound after cleaning reaction.
Specifically, the compound after the cleaning reaction specifically includes:
Cleaning solution is put into reaction zone, the compound after cleaning reaction；Or
So that the compound after reaction is entered cleaning area by air pump 22, and cleaning solution is put into cleaning area, cleaning reaction
Resulting composite afterwards.
It is individually mixed under nonreactive empty in the homogeneous magnetic standard configuration body of liquid with solid-state tagged ligand, this implementation can be used
Example.By the present invention in that with the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and the storage homogeneous magnetic standard configuration body of liquid is set
Liquid homogeneous magnetic standard configuration body storage unit when detection, makes the sample three of liquid homogeneous magnetic standard configuration body and solid-state tagged ligand and addition
Person is sufficiently mixed, and can effectively improve the speed of reaction, to improve the sensitivity of detection, repeatability and accuracy.This
Outside, sample is mixed with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand in reaction zone, single step reaction, improves detection efficiency, and logical
Over cleaning liquid cleans magnetic bead, removes the object of the analyte of non-specific adsorption, luminous agent marker and other influences testing result
Matter can further increase the precision of detection.
Embodiment nine
As shown in Figure 4, Figure 5, the embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, institute
Stating reaction zone includes interconnected the first reaction subregion 241 and the second reaction subregion 242, and first reacts subregion 241 and institute
The connection of sample-adding portion 21 is stated, solid-state tagged ligand is placed on the first reaction subregion, which comprises
Sample is added from sample-adding portion 21 and sample is made to enter the first reaction subregion 241；
The sample and solid-state tagged ligand is reacted in subregion 241 first by air pump 22 to be sufficiently mixed, react, obtain
To tagged ligand compound；
Tagged ligand compound is put into the second reaction subregion 242；
The homogeneous magnetic standard configuration body of liquid is put into the second reaction subregion 242, keeps the tagged ligand compound by air pump 22
Object and the homogeneous magnetic standard configuration body of liquid react in subregion 242 second to be sufficiently mixed, reacts, and resulting composite is obtained；
Resulting composite after cleaning reaction.
In the present invention, first reaction subregion 241, first react subregion 242 can be one for reaction type chamber, can also
To be some for sharing interconnecting piece 27.
Specifically, the compound after cleaning reaction specifically includes:
Cleaning solution is put into the second reaction subregion 242, the resulting composite after cleaning reaction；Or
Resulting composite after reaction enters cleaning area 29, and cleaning solution is put into cleaning area, after cleaning reaction most
Whole compound.
The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and it is homogeneous that storage liquid is arranged
The homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand is not used in chip in the homogeneous magnetic standard configuration body storage unit of the liquid of magnetic standard configuration body
When separate, when detection, make the sample elder generation hybrid reaction of solid-state tagged ligand and addition, then mix instead with the homogeneous magnetic standard configuration body of liquid
It answers, is sufficiently mixed three, can react more abundant, and reduce other compounds, to improve the sensitivity of detection, repeat
Property and accuracy.In addition, clean magnetic bead by cleaning solution, remove the analyte of non-specific adsorption, luminous agent marker and its
He influences the substance of testing result；The precision of detection can be further increased.
Embodiment ten
As shown in figs. 4 and 6, the embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, institute
Stating reaction zone includes interconnected the first reaction subregion 241 and the second reaction subregion 242, and the first reaction subregion adds with described
Sample portion 21 is connected to, and solid-state tagged ligand is placed on the second reaction subregion, which comprises
Sample is added from sample-adding portion 21 and sample is made to enter the first reaction subregion；
The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic of liquid are made by air pump 22
Standard configuration body is sufficiently mixed in the first reaction subregion, reacts, and obtains magnetic standard configuration nanocrystal composition；
Magnetic standard configuration nanocrystal composition is put into the second reaction subregion；
By air pump 22 make the magnetic standard configuration nanocrystal composition and solid-state tagged ligand second react in subregion be sufficiently mixed,
Reaction, obtains resulting composite；
Resulting composite after cleaning reaction.
The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and it is homogeneous that storage liquid is arranged
The homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand is not used in chip in the homogeneous magnetic standard configuration body storage unit of the liquid of magnetic standard configuration body
When separate, when detection, make the sample elder generation hybrid reaction of the homogeneous magnetic standard configuration body of liquid and addition, then mix instead with solid-state tagged ligand
It answers, is sufficiently mixed three, can react more abundant, and reduce other compounds, to improve the sensitivity of detection, repeat
Property and accuracy.In addition, clean magnetic bead by cleaning solution, remove the analyte of non-specific adsorption, luminous agent marker and its
He influences the substance of testing result；The precision of detection can be further increased.
Embodiment 11
As shown in Fig. 4, Fig. 7, the embodiment of the present invention also provides a kind of reaction method of luminous micro-fluidic chip of magnetic particle, institute
Stating reaction zone includes interconnected the first reaction subregion and the second reaction subregion, and first reacts subregion and the sample-adding portion 21
Connection, solid-state tagged ligand are placed on the second reaction subregion, which comprises
Sample is added from sample-adding portion 21 and sample is made to enter the first reaction subregion；
The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic of liquid are made by air pump 22
Standard configuration body is sufficiently mixed in the first reaction subregion, reacts, and obtains magnetic standard configuration nanocrystal composition；
Magnetic standard configuration nanocrystal composition after cleaning reaction；
Magnetic standard configuration nanocrystal composition after cleaning is put into the second reaction subregion；
By air pump 22 make the magnetic standard configuration nanocrystal composition and solid-state tagged ligand second react in subregion be sufficiently mixed,
Reaction, obtains resulting composite.
The embodiment of the present invention is by using the homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand, and it is homogeneous that storage liquid is arranged
The homogeneous magnetic standard configuration body of liquid and solid-state tagged ligand is not used in chip in the homogeneous magnetic standard configuration body storage unit of the liquid of magnetic standard configuration body
When separate, when detection, make the sample elder generation hybrid reaction of the homogeneous magnetic standard configuration body of liquid and addition, then mix instead with solid-state tagged ligand
It answers, is sufficiently mixed three, can react more abundant, and reduce other compounds, to improve the sensitivity of detection, repeat
Property and accuracy.In addition, clean magnetic bead by cleaning solution, remove the analyte of non-specific adsorption, luminous agent marker and its
He influences the substance of testing result；The precision of detection can be further increased.
In addition, the solid-state tagged ligand can with the homogeneous magnetic mark ligand binding (such as double antibody sandwich method) of liquid or with mark
Remember Ligand Competition (such as competition law).Wherein the ligand of the ligand of luminous agent label and enzyme label can be with the homogeneous magnetic standard configuration body of liquid
Ligand it is identical, can also be different.Preferably, in one embodiment of the invention, selecting two kinds of different antibodies as solid
State tagged ligand and the homogeneous magnetic standard configuration body of liquid are with double antibody sandwich method detection and analysis object.In another embodiment of the invention,
A kind of antigen and a kind of antibody are selected, respectively as solid-state tagged ligand and the homogeneous magnetic standard configuration body of liquid, sample is detected with competition law
This.Detection zone 28 is set, convenient for resulting composite being moved to detection zone 28 and is observed and is examined after cleaning solution being cleaned
It surveys, is easy to use, it is simple and convenient.Micro-fluidic chip of the invention will test all reagent components needed for process, and (liquid is homogeneous
Magnetic standard configuration body, solid-state tagged ligand, cleaning solution, luminescent solution etc.) it integrates, be built into micro-fluidic chip, and by ingenious micro-
Channel design realizes that the operating in a key of micro-fluidic chip (only need to be can be achieved with examining by start button under the operation of necessary instrument
Survey, be not necessarily to complex operations), whole blood separation, immune response, cleaning separation, chemiluminescence detection are realized, so as to avoid existing micro-
Structure design is simple in fluidic chip, detection when it is complicated for operation the deficiencies of and defect.Also overcoming traditional chemical light-emitting appearance can only
The shortcomings that carrying out serum or blood plasma detection, and whole blood sample cannot being detected.
The present invention is not simple superposition magnetic microparticle chemiluminescence technology and microfluidic chip technology, but passes through hydraulic seal
Design, channel design, integrate the required all chemical constituents of detection, are built into micro-fluidic chip, and with magnet active drive,
Realize one-touch magnetic microparticle chemiluminescence immune detection, thus in portable necessary instrument realize whole blood in analyte it is fast
Speed, highly sensitive, accurate quantitative analysis detection.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (10)
- The micro-fluidic chip 1. a kind of magnetic particle shines, which is characterized in that the chip includes:Substrate；Sample-adding portion being disposed on the substrate, being added for sample；It the homogeneous magnetic standard configuration body storage unit of the liquid being disposed on the substrate and is stored in the homogeneous magnetic standard configuration body storage unit of the liquid The homogeneous magnetic standard configuration body of liquid；Solid-state tagged ligand；Air pump on the substrate is set；The reaction zone for being disposed on the substrate, being connected to the sample-adding portion, the reaction zone is for sample and the homogeneous magnetic standard configuration of liquid Body, solid-state tagged ligand, which generate, to be mixed and reacts；Cleaning solution storage unit and the cleaning solution being stored in the cleaning solution storage unit；The homogeneous magnetic standard configuration body of liquid includes magnetic bead, temperature-sensitive material and solution；Between the reaction zone and the sample-adding portion, between the reaction zone and the homogeneous magnetic standard configuration body storage unit of the liquid, institute It states and is provided with interconnecting piece between reaction zone and the cleaning solution storage unit；The solid-state tagged ligand is arranged in the reaction zone, is in the homogeneous magnetic standard configuration body storage unit of the liquid or described anti- It answers in the interconnecting piece between area and the homogeneous magnetic standard configuration body storage unit of the liquid.
- The micro-fluidic chip 2. magnetic particle as described in claim 1 shines, which is characterized in that the solid-state tagged ligand includes enzyme Or the ligand of luminous agent label；The enzyme includes: one of horseradish peroxidase and alkaline phosphatase or a variety of；The luminous agent include: acridinium ester, One of ABEI, fluorescent dye, fluorescin and fluorescent microsphere are a variety of.
- The micro-fluidic chip 3. magnetic particle as claimed in claim 2 shines, which is characterized in that the chip further include:The detection zone being connected to the reaction zone；Luminescent solution storage unit and the luminescent solution being stored in luminescent solution storage unit；Connection is provided between the reaction zone and the detection zone, between the luminescent solution storage unit and the detection zone Portion.
- The micro-fluidic chip 4. magnetic particle as claimed in claim 3 shines, which is characterized in that the sample-adding portion, the homogeneous magnetic of liquid It is adopted at standard configuration body storage unit, reaction zone, detection zone, cleaning solution storage unit, luminescent solution storage unit and each interconnecting piece at least one With micro- channel structure, it is micro-meter scale that micro- channel is at least one-dimensional.
- 5. a kind of reaction method using the luminous micro-fluidic chip of the described in any item magnetic particles of Claims 1 to 4, feature exist In when the solid-state tagged ligand is arranged in the reaction zone, which comprisesSample is added from sample-adding portion and sample is made to enter reaction zone；The homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit of liquid is put into reaction zone；Sample is set to be sufficiently mixed, react in reaction zone with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand by air pump；Compound after cleaning reaction.
- 6. a kind of reaction method using the luminous micro-fluidic chip of the described in any item magnetic particles of Claims 1 to 4, feature exist It is arranged in the homogeneous magnetic standard configuration body storage unit of the liquid or the reaction zone and the liquid in, the solid-state tagged ligand When interconnecting piece between homogeneous magnetic standard configuration body storage unit, which comprisesSample is added from sample-adding portion and sample is made to enter reaction zone；It is put into after the homogeneous magnetic standard configuration body of liquid in the homogeneous magnetic standard configuration body storage unit of liquid is mixed with solid-state tagged ligand anti- Answer area；Sample is set to be sufficiently mixed, react in reaction zone with the homogeneous magnetic standard configuration body of liquid, solid-state tagged ligand by air pump；Compound after cleaning reaction.
- 7. a kind of reaction method using the luminous micro-fluidic chip of the described in any item magnetic particles of Claims 1 to 4, feature exist In the reaction zone includes interconnected the first reaction subregion and the second reaction subregion, and the solid-state tagged ligand is placed In the first reaction subregion, which comprisesSample is added from sample-adding portion and sample is made to enter the first reaction subregion；The sample and solid-state tagged ligand is reacted in subregion first by air pump to be sufficiently mixed, react, obtain label and match Nanocrystal composition；Tagged ligand compound is put into the second reaction subregion；The homogeneous magnetic standard configuration body of liquid is put into the second reaction subregion, keeps the tagged ligand compound and liquid equal by air pump Phase magnetic standard configuration body is sufficiently mixed in the second reaction subregion, reacts, and obtains resulting composite；Resulting composite after cleaning reaction.
- 8. reaction method as claimed in claim 7, which is characterized in that the reaction zone is equipped with cleaning area；The cleaning reaction Compound afterwards specifically includes:Cleaning solution is put into the second reaction subregion, the resulting composite after cleaning reaction；OrResulting composite after reaction enters cleaning area, and cleaning solution is put into cleaning area, final compound after cleaning reaction Object.
- 9. a kind of reaction method using the luminous micro-fluidic chip of the described in any item magnetic particles of Claims 1 to 4, feature exist In the reaction zone includes interconnected the first reaction subregion and the second reaction subregion, and the solid-state tagged ligand is placed In the second reaction subregion, which comprisesSample is added from sample-adding portion and sample is made to enter the first reaction subregion；The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic standard configuration body of liquid are made by air pump It is sufficiently mixed, reacts in the first reaction subregion, obtain magnetic standard configuration nanocrystal composition；Magnetic standard configuration nanocrystal composition is put into the second reaction subregion；The magnetic standard configuration nanocrystal composition and solid-state tagged ligand is reacted in subregion second by air pump to be sufficiently mixed, react, Obtain resulting composite；Resulting composite after cleaning reaction.
- 10. a kind of reaction method using the luminous micro-fluidic chip of the described in any item magnetic particles of Claims 1 to 4, feature Be, the reaction zone includes interconnected first reaction subregion and the second reaction subregion, and the first reaction subregion with it is described The connection of sample-adding portion, the solid-state tagged ligand are placed in the second reaction subregion, which comprisesSample is added from sample-adding portion and sample is made to enter the first reaction subregion；The homogeneous magnetic standard configuration body of liquid is put into the first reaction subregion, the sample and the homogeneous magnetic standard configuration body of liquid are made by air pump It is sufficiently mixed, reacts in the first reaction subregion, obtain magnetic standard configuration nanocrystal composition；Magnetic standard configuration nanocrystal composition after cleaning reaction；Magnetic standard configuration nanocrystal composition after cleaning is put into the second reaction subregion；The magnetic standard configuration nanocrystal composition and solid-state tagged ligand is reacted in subregion second by air pump to be sufficiently mixed, react, Obtain resulting composite.
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| CN107930710A (en) * | 2017-11-27 | 2018-04-20 | 深圳华炎微测医疗科技有限公司 | Chemiluminescence testing microfluid control chip and chemiluminescence testing microfluid control chip system and their application |
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| WO2021068912A1 (en) * | 2019-10-11 | 2021-04-15 | 深圳华迈兴微医疗科技有限公司 | Magnetic particle luminescence micro-fluidic chip for multi-marker detection, and detection device |
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Application publication date: 20190906 |