CN109709349A - A kind of chemiluminescence immunoassay system - Google Patents
A kind of chemiluminescence immunoassay system Download PDFInfo
- Publication number
- CN109709349A CN109709349A CN201910170361.3A CN201910170361A CN109709349A CN 109709349 A CN109709349 A CN 109709349A CN 201910170361 A CN201910170361 A CN 201910170361A CN 109709349 A CN109709349 A CN 109709349A
- Authority
- CN
- China
- Prior art keywords
- filling
- chip
- area
- detection
- chemiluminescence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000003018 immunoassay Methods 0.000 title claims abstract description 20
- 238000001514 detection method Methods 0.000 claims abstract description 48
- 238000011049 filling Methods 0.000 claims abstract description 47
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 43
- 239000007788 liquid Substances 0.000 claims abstract description 27
- 238000003860 storage Methods 0.000 claims abstract description 16
- 239000002699 waste material Substances 0.000 claims abstract description 15
- 230000005611 electricity Effects 0.000 claims abstract description 13
- 238000002038 chemiluminescence detection Methods 0.000 claims abstract description 11
- 238000000926 separation method Methods 0.000 claims abstract description 11
- 238000007885 magnetic separation Methods 0.000 claims abstract description 7
- 230000003287 optical effect Effects 0.000 claims abstract description 6
- 239000000945 filler Substances 0.000 claims description 29
- 238000004140 cleaning Methods 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 239000011324 bead Substances 0.000 claims description 17
- 238000010521 absorption reaction Methods 0.000 claims description 14
- 238000011534 incubation Methods 0.000 claims description 11
- 238000002203 pretreatment Methods 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 8
- 230000002209 hydrophobic effect Effects 0.000 claims description 7
- 230000003075 superhydrophobic effect Effects 0.000 claims description 5
- 239000003365 glass fiber Substances 0.000 claims description 3
- 239000004745 nonwoven fabric Substances 0.000 claims description 3
- 229920006267 polyester film Polymers 0.000 claims description 3
- 238000007689 inspection Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000008595 infiltration Effects 0.000 abstract 1
- 238000001764 infiltration Methods 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 35
- 238000000034 method Methods 0.000 description 13
- 238000013461 design Methods 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 8
- 238000010586 diagram Methods 0.000 description 7
- 238000002156 mixing Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000005284 excitation Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- -1 amino, carboxyl Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000012502 diagnostic product Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 239000007772 electrode material Substances 0.000 description 1
- 238000005370 electroosmosis Methods 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000000567 greater sac Anatomy 0.000 description 1
- 230000003760 hair shine Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
Landscapes
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Optical Measuring Cells (AREA)
Abstract
The invention discloses a kind of chemiluminescence immunoassay systems, including liquid-transfering device, temperature control device, magnetic separation device, optical detection device, sample reagent storage device and the electricity to moisten micro-fluidic chemiluminescence detection chip.Electricity moistens micro-fluidic chemiluminescence detection chip according to electric infiltration phenomenon, apply the electrode voltage sequence being pre-designed by the electrod-array at the die substrate back side, so that the drop of chip surface is moved between each functional areas of chip surface according to scheduled path, and drop separation can be carried out in functional areas and mixes operation.Liquid-transfering device is used for from sample reagent storage device mobile reagent to filling area, and from waste liquid memory block removes waste liquid.Compared to traditional equipment, the cost of the batch detection of multisample or the joint-detection of the more reagents of single sample can be really realized on one chip.
Description
Technical field
The present invention relates to chemiluminescence detection fields, and in particular to a kind of chemiluminescence immunoassay system.
Background technique
Chemiluminescence is the light radiation generated by chemical reaction.Chemiluminescence analysis has high sensitivity, selection
Property it is preferable, instrument is simple, analysis speed is fast, the range of linearity can wide the advantages that reaching several orders of magnitude, in environment, life, medicine etc.
Field obtains more and more extensive application.The essential distinction of chemiluminescence and other luminesceence analyses is that system generates (the light spoke that shines
Penetrate) the energy source that is absorbed is different.System generates chemiluminescence, it is necessary to have one generates the light radiation reaction that can examine signal
The chemical reaction for leading to the independent reaction step of the enough energy of luminescence phenomenon can be once provided with one.
Currently, the micromation of chemiluminescence diagnostic products, is typically based on micro-fluidic chip.Microfluidic chip technology
It (Microfluidics) is basic operations such as biology, chemistry, the sample preparation of medical analysis process, reaction, separation, detections
Unit is integrated on the chip of one piece of micro-meter scale, is automatically performed analysis overall process.Micro-fluidic chip uses similar semiconductor
Micro electro mechanical processing technology constructs microflow path system on chip, by experiment with analytic process reprint to by communication with one another path and
On the chip structure of liquid phase cell composition, after loading biological sample and reaction solution, using micromechanics pump, electric hydraulic pump and electroosmotic flow
The methods of the flowing of buffer in driving chip, microfluidic circuit is formed, in carrying out a kind of or continuous a variety of reaction on chip.Laser
A variety of detection systems such as induced fluorescence, electrochemistry and chemistry and many detection means in conjunction with the analysis means such as mass spectrum are
It is used in micro-fluidic chip, quick, accurate and high throughput analysis is carried out to sample.The maximum feature of micro-fluidic chip is one
The micro-total analysis system of the numerous compound system of Multifunctional centralized architectonical sum number mesh can be formed on a chip.Microreactor is
In chip lab commonly be used for biochemical reaction structure, as Capillary Electrophoresis, polymerase chain reaction, enzyme reaction and
The microreactor etc. of DNA hybridization reaction.Therefore, chip often designs complexity, higher cost, is difficult to mass production.
Magnetic bead refers to that magnetic nano-particle formed in conjunction with inorganic or organic molecule is dispersed in certain base fluid
Colloidal state composite material with high stability.Since magnetic bead has a magnetic responsiveness, at low cost, less energy consumption and pollution-free etc. special
Point, people in magnetic bead surfaces or by the functional group of magnetic bead surfaces, such as amino, carboxyl, sulfydryl and ethylene oxide, by enzyme,
The bioactive substances such as antibody, oligonucleotides are fixed, and can be further used for enzyme immobilizatio, target medicine carrier, cell
Sorting, immune detection, albumen and nucleic acid isolate and purify and the fields such as hybridization check.Traditional immunology detection is mostly with ELISA Plate
For solid phase carrier, suspension magnetic bead as carrier specific surface area with higher, can substantially more with example reaction, in addition
The flexible Application of externally-applied magnetic field has higher sensitivity, faster detection speed compared with ELISA Plate carrier and preferably repeats
Property the advantages that, be widely used at present biology and medicine detection etc. fields.
Summary of the invention
Goal of the invention: being directed to the above-mentioned prior art, propose a kind of chemiluminescence immunoassay system, reduces a kind of chemistry hair
The design and preparation cost of light immunoassay system.
Technical solution: a kind of chemiluminescence immunoassay system, including liquid-transfering device, temperature control device, magnetic separation device,
Optical detection device, sample reagent storage device and the electricity moisten micro-fluidic chemiluminescence detection chip;Wherein:
It includes the cavity formed by bottom plate and cover board that the electricity, which moistens micro-fluidic chemiluminescence detection chip, the cavity quilt
Several functional areas are divided into, the functional areas include filling area, cleaning Disengagement zone, incubation reaction area, light detection area, waste liquid storage
Area;Connection path is equipped between the functional areas, the plate upper surface where the functional areas and the connection path is laid
Electrod-array, the electrod-array surface coat hydrophobic/super-hydrophobic coat;
The liquid-transfering device is used for from the sample reagent storage device mobile reagent to the filling area, and from institute
It states waste liquid memory block and removes waste liquid;
The temperature control device is used to control the temperature in the incubation reaction area;
Separation control is carried out to magnetic bead the magnetic separation device is for carrying out magnetic bead cleaning in the cleaning Disengagement zone when;
The optical detection device is used to collect the photon issued when light detection chemiluminescence reaction.
Further, the cover board of filling area's face is equipped with filler port, before the top of the filler port is equipped with filling
Processing component, the filling pre-treatment component include the filling channel for being connected to the filling area, are equipped with and inhale in the filling channel
It is attached to use filler assembly.
Further, the unit plane of each functional areas is adjusted by the way that the local height of each functional areas of cover board face is arranged
The corresponding liquid containing amount of product.
Further, the position in light detection area described in the cover board face is set as convex lens structures.
Further, the quantity of the filler port is greater than 1.
Further, the absorption with filler assembly be polyester film, glass fibre element film, cellulosic filter paper, in non-woven fabrics
One or more materials be made.
Further, the absorption is using microballon made of hydrophilic material, and on the microballon with filler assembly
Connection is for combining the conjugate of molecule to be filtered.
Further, the filling channel vertically connects the cover board, is equipped with atmospheric equilibrium in the filling channel side
Through-hole, the atmospheric equilibrium through-hole are located at below the position of the absorption filler assembly.
The utility model has the advantages that chemiluminescence immunoassay system of the invention moistens micro-fluidic chemiluminescence detection core using electricity
Piece, chip infiltrate (electowetting) phenomenon according to electricity, apply the electrode being pre-designed by the electrod-array at the bottom plate back side
Contact potential series, so that the drop of chip surface is moved between each functional areas of chip surface according to scheduled path, and
Drop separation can be carried out in functional areas and mixes operation, and compared to traditional micro-fluidic chip, chip surface does not have to design
Complicated pipeline, Micropump/micro-valve with preparation, structure is simple, designs and prepares cost and is far below traditional micro-fluidic chip.Phase
Knot is passed through since chip surface eliminates complicated pipeline, Micropump/micro-valve for traditional chemiluminescence immunoassay system
The batch detection of multisample or the joint-detection of the more reagents of single sample can really be realized by closing liquid-transfering device, and based on traditional
This function only theoretically may be implemented in the chemiluminescence immunoassay system of micro-fluidic chip, in actual design and prepares this
When the micro-fluidic chip of class function, often design difficulty is big, and reagent, which encapsulates, requires high, technique difficulty to realize, to lack centainly
Practicability.
Detailed description of the invention
Fig. 1 is chemiluminescent analyzer structural schematic diagram;
Fig. 2 is the chip surface structural schematic diagram for the more reagent joint-detections of single sample;
Fig. 3 is the chip surface structural schematic diagram for multisample batch detection;
Fig. 4 is filling one schematic diagram of pre-treatment component working method;
Fig. 5 is filling two schematic diagram of pre-treatment component working method;
Fig. 6 is the structural schematic diagram of cover board face light detection zone position;
Fig. 7 is this chemiluminescent analyzer single testing process schematic diagram.
Specific embodiment
Further explanation is done to the present invention with reference to the accompanying drawing.
As shown in Figure 1, a kind of chemiluminescent analyzer, including the inspection of liquid-transfering device 5, temperature control device, magnetic separation device, light
It surveys device 4, sample reagent storage device 6 and electricity and moistens micro-fluidic chemiluminescence detection chip 7.Wherein:
It includes the cavity formed by bottom plate and cover board that electricity, which moistens micro-fluidic chemiluminescence detection chip 7, and cavity is divided into
Several functional areas, functional areas include filling area, cleaning Disengagement zone, incubation reaction area, light detection area, waste liquid memory block, by setting
The corresponding liquid containing amount of the unit area for setting the local height of each functional areas of cover board face to adjust each functional areas.Functional areas it
Between be equipped with connection path, plate upper surface where functional areas and connection path lays hydrophobic/super-hydrophobic coat, hydrophobic/super
Electrod-array is laid under hydrophobic coating.Usually select copper as electrode material, electrode size is generally 1.5mm × 1.5mm, core
Piece baseboard material is typically chosen FR4.
The cover board for filling area's face is equipped with several filler ports, and the top of filler port is equipped with filling pre-treatment component, such as
Shown in Fig. 2, Fig. 3, filler port has ten.As shown in Figure 4, Figure 5, filling pre-treatment component includes that the filling in connection filling area is logical
Road 1 fills the vertical connecting cover plate in channel 1, fills and is equipped with absorption filler assembly 2 in channel, is equipped in filling channel side big
Gas balances through-hole 3, and atmospheric equilibrium through-hole 3 is located at below the position of absorption filler assembly 2.
Filling of the filler port for sample, reagent, excitation reagent, cleaning solution etc..Absorption is used for absorption sample with filler assembly
Specific components in this, such as: the interception filtering for the above particulate matter of the micron orders such as haemocyte or fibrin aggressiveness can be with
It is made, is also possible to above-mentioned using one of polyester film, glass fibre element film, cellulosic filter paper and non-woven fabrics or multiple material
Coagulant, haemocyte membrane antibody are added in material;For the interception of certain specific molecular, the hydrophilies material such as agarose can be used
Microballon made of expecting, and conjugate of the connection for combination molecule to be filtered on microballon.The surrounding of filler assembly 2 can be embedded in
1 side wall of channel is filled, or is supported by there is the porous structure of some strength.As shown in Figure 4, Figure 5, sample adds from top
It adds in filling channel 1, under conditions of gravity or external application air pressure, sample can penetrate into filler assembly 2, therein
Specific components can be adsorbed by filler assembly 2, and the group branch for being more suitable for detection in addition flows into after passing through filler assembly 2 from filling
Hole enters in the filling area on bottom plate, realizes the pre-treatment and filling of sample.
As shown in Figure 2 and Figure 3, connection path is equipped between each functional areas, connection path can be the side of several unit areas
The continuous path of block composition, is correspondingly arranged an electrode in the corresponding lower surface of base plate of the square of each unit area.Each function
Area can be equally made of the square of several unit areas, and same its is correspondingly arranged on electrod-array.Similarly, each functional areas
And the electrode of multiple array arrangements can also be correspondingly arranged under the square of the unit area of continuous path, so as to improve drop shifting
The precision or efficiency of dynamic, mixing etc..
Droplet size is determined by the height of electrode area and cavity in chip, one timing of electrode area, single electrode area
Corresponding droplet size increases with housing depth and is become larger, therefore can be accommodated more by tuning up housing depth when chip design
More drops, to reduce chip area, the height of general cavity is no more than 0.5mm.
Liquid-transfering device is used for the mobile reagent from sample reagent storage device and removes to filling area, and from waste liquid memory block
Waste liquid.Liquid-transfering device hardware is mainly made of sample needle, fluid line, pump valve and movement mechanism, and movement mechanism drives sample needle
Carry out horizontal and elevating movement, filling area and waste liquid memory block in operation area Covering samples reagent storage means, chip.Fortune
Motivation structure drives sample needle to be moved to sample reagent storage device and draws a certain amount of sample or reagent, generally in 5ul or more, so
It is moved to above the filler port of chip afterwards, the liquid of absorption is discharged, realize the first of sample, reagent, excitation reagent, cleaning solution etc.
Step distribution, and waste liquid in the chip of waste liquid memory block is emptied with liquid-transfering device.
Temperature control device is located at the incubation reaction area back side of chip, and incubation reaction area temperature is controlled the temperature value in setting.
Temperature control device can be using the heating device being mounted on instrument, such as resistance wire or semiconductor heat electric refrigerator etc. and temperature
The closed-loop control system that sensor is formed is to guarantee temperature stable on chip;Heating device and temperature sensor can also be integrated
It, can more accurate effective control temperature although chip cost increased in this way on chip.Chemiluminescence incubation reaction
Temperature general control at 37 ± 0.5 DEG C.
Magnetic separation device carries out carrying out separation control to magnetic bead when magnetic bead cleaning for cleaning in Disengagement zone.Separating mechanism
Positioned at the cleaning Disengagement zone back side of chip.Its hardware body be permanent magnet, by adjusting the distance between chip of permanent magnet,
Or the power on/off by electromagnet, the magnetic field of control chip cleaning Disengagement zone are strong and weak.For the adsorption effect for guaranteeing magnetic bead, usually select
Ndfeb magnet or electromagnet are taken, magnetic field strength is generally 4000 Gauss.
As shown in fig. 6, the position in the cover board face light detection area of chip is set as convex lens structures, convenient for aggregation light letter
Number.Optical detection device 4 is located above the light detection area of chip, for collecting the light issued when the reaction of light detection chemiluminescence
Son.Light detection generally uses the photoelectric devices such as photomultiplier tube, photocell as light signal collection element.
Sample reagent storage device is mainly used for storing sample and reagent, when necessary containing temperature control system with guarantee sample and
The storage temperature of reagent requires, or guarantees the mixing of heterogeneous reagent containing mechanical reciprocation device.This sample reagent
Storage device can place a certain number of samples and kit, to meet continuous detection, the entry detection of instrument system.
Single testing process includes sample-adding, liquid relief, mixing, incubation, six cleaning separation, light detection steps, such as Fig. 7 institute
Show, specifically:
1) it is loaded: required sample, reagent, silicone oil etc. is filled into the filling area of chip by liquid-transfering device.When sample-adding
Further include online Sample pretreatment step, i.e., after sample is equipped with filling pre-treatment component by the top of filler port, component occurs
Separation so that be more suitable for detection sample components stay in filling area bottom electrode above.
2) liquid relief: the phenomenon that being infiltrated according to electricity, hydrophobic/super-hydrophobic coat of chip surface is passed through high pressure in corresponding electrode
After electricity, hydrophobic/super-hydrophobic coat can become than more hydrophilic, and the capillary phenomenon generated using surface tension, liquid can flow to connection
The electrode of high pressure.By a series of electrode voltage sequence of pre-programmeds, liquid can be mobile in chip surface by scheduled path.It is logical
The contact potential series of design pressor areas electrode is crossed, drop needed for experiment being isolated from the sample or reagent in filling area, or
Drop in each functional areas is moved to required position.
3) mix: isolated drop can be in chip top with procedure script, i.e., predefined electrode voltage sequence definition
Mode move.Procedure script only needs sample/reagent needed for reaction being moved to same position, they will merge automatically
At a bigger drop, then even separates and merge again again in different directions reciprocating motion, pitch of the laps operation, so that it may is real
Now mix.
4) incubate: control drop is moved to incubation reaction area and is sufficiently reacted, after the reaction time for reaching setting, by liquid
Drop is moved to cleaning Disengagement zone.
5) cleaning separation: when separation, control magnet, which moves upwards, to be close to chip lower layer or controls electromagnet be powered, by magnetic bead
It is adsorbed on chip surface, control drop removes cleaning Disengagement zone, and under extremely strong magnetic field, small magnetic bead will be gathered into very
Close magnet, and cannot be taken away by drop, thus realize that magnetic bead is separated with unreacted dissociant.When cleaning, control
Magnet moves downward or controls electromagnet power-off, and magnetic field disappears, and mobile cleaning drop is mixed with the magnetic bead after separating, by magnetic
The unreacted dissociant being mingled in pearl is discharged into cleaning drop.Repeated isolation, cleaning process will test in drop not
The dissociant of reaction sufficiently washs.
6) light detection: mobile excitation reagent, excitation reagent is usually exciting liquid or substrate, after exciting reagent droplet and cleaning
Magnetic bead combine and mix, the drop after mixing is moved to light detection area, the photon that acquisition reaction issues.
7) drop that detection is completed is moved to waste liquid memory block.
Electricity moistens micro-fluidic chemiluminescence detection chip and needs according to the more reagent joint-detections of single sample or multisample batch
Amount detection carrys out the connection path between the position of each functional areas and size in design chips, and each functional areas of design.Entry
When joint-detection or multisample batch detection:
1) sample S and reagent R1, R2, R3, R4, R5 are filled from sample reagent storage device to the filling area of chip, such as
Shown in Fig. 1;Or sample S1, S2, S3, S4, S5, S6, S7, S8 and reagent R fill adding to chip from sample reagent storage device
Area is infused, as shown in Figure 2.Reagent R1 is generally made of 3 kinds of reagent components, and component 1 is R1-1, and component 2 and 3 can be added to simultaneously
One filler port forms R1-23.
2) according to time beat, such as 20s, come carry out one by one liquid relief, mix complete detection drop TEST1, TEST2,
TEST3。
3) drop after mobile mixing incubates scheduled duration to incubation reaction area;
4) after reaching incubative time, mobile drop to cleaning Disengagement zone, using formed after the cleaning of W drop TEST1 ',
TEST2',TEST3';W drop is cleaning reagent.
5) separation T drop forms TEST1 ", TEST2 ", TEST3 " with the detection droplets mixing after cleaning, and moves respectively
Light detection is carried out to detection zone;T drop is to excite reagent.
6) drop that detection is completed is moved to waste liquid memory block.
Above-mentioned steps 2), 4), 5) in the number of drops that is formed according to detection type, sample number it is different and different.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of chemiluminescence immunoassay system, which is characterized in that including liquid-transfering device, temperature control device, magnetic separation device,
Optical detection device, sample reagent storage device and the electricity moisten micro-fluidic chemiluminescence detection chip;Wherein:
It includes the cavity formed by bottom plate and cover board that the electricity, which moistens micro-fluidic chemiluminescence detection chip, and the cavity is divided
At several functional areas, the functional areas include filling area, cleaning Disengagement zone, incubation reaction area, light detection area, waste liquid memory block;
Connection path is equipped between the functional areas, the plate upper surface where the functional areas and the connection path lays electrode
Array, the electrod-array surface coat hydrophobic/super-hydrophobic coat;
The liquid-transfering device is used for the mobile reagent from the sample reagent storage device and gives up to the filling area, and from described
Remove waste liquid in liquid memory block;
The temperature control device is used to control the temperature in the incubation reaction area;
Separation control is carried out to magnetic bead the magnetic separation device is for carrying out magnetic bead cleaning in the cleaning Disengagement zone when;
The optical detection device is used to collect the photon issued when light detection chemiluminescence reaction.
2. chemiluminescence immunoassay system according to claim 1, it is characterised in that: the cover board of filling area's face
It is equipped with filler port, the top of the filler port is equipped with filling pre-treatment component, and the filling pre-treatment component includes connection institute
The filling channel in filling area is stated, is equipped with absorption filler assembly in the filling channel.
3. chemiluminescence immunoassay system according to claim 1, it is characterised in that: by the way that the cover board face is arranged
The local height of each functional areas is come the corresponding liquid containing amount of unit area that adjusts each functional areas.
4. chemiluminescence immunoassay system according to claim 1, it is characterised in that: the inspection of light described in the cover board face
The position for surveying area is set as convex lens structures.
5. chemiluminescence immunoassay system according to claim 2, it is characterised in that: the quantity of the filler port is greater than
1。
6. chemiluminescence immunoassay system according to claim 2 or 5, it is characterised in that: absorption filler group
Part is made of one of polyester film, glass fibre element film, cellulosic filter paper, non-woven fabrics or multiple material.
7. chemiluminescence immunoassay system according to claim 2 or 5, it is characterised in that: absorption filler group
Part is that connection is used to combine the conjugate of molecule to be filtered using microballon made of hydrophilic material, and on the microballon.
8. chemiluminescence immunoassay system according to claim 2 or 5, it is characterised in that: the filling channel is vertical
The cover board is connected, is equipped with atmospheric equilibrium through-hole in the filling channel side, the atmospheric equilibrium through-hole is located at the absorption
Below the position of filler assembly.
9. chemiluminescence immunoassay system according to claim 6, it is characterised in that: the filling channel vertically connects
The cover board is equipped with atmospheric equilibrium through-hole in the filling channel side, and the atmospheric equilibrium through-hole is located at the absorption with filling out
Below the position for expecting component.
10. chemiluminescence immunoassay system according to claim 7, it is characterised in that: the filling channel vertically connects
The cover board is connect, is equipped with atmospheric equilibrium through-hole in the filling channel side, the atmospheric equilibrium through-hole is located at absorption use
Below the position of filler assembly.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910170361.3A CN109709349B (en) | 2019-03-07 | 2019-03-07 | Chemiluminescent immunoassay system |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910170361.3A CN109709349B (en) | 2019-03-07 | 2019-03-07 | Chemiluminescent immunoassay system |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109709349A true CN109709349A (en) | 2019-05-03 |
CN109709349B CN109709349B (en) | 2024-02-06 |
Family
ID=66266559
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910170361.3A Active CN109709349B (en) | 2019-03-07 | 2019-03-07 | Chemiluminescent immunoassay system |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109709349B (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110286120A (en) * | 2019-08-15 | 2019-09-27 | 北京农业质量标准与检测技术研究中心 | Flow-type electrochemical luminescence biological detection system |
CN110755699A (en) * | 2019-09-18 | 2020-02-07 | 浙江省北大信息技术高等研究院 | Implantable electroosmotic micropump device |
CN110885907A (en) * | 2019-12-13 | 2020-03-17 | 福建工程学院 | Full-automatic sample adding, hybridizing and detecting method for HPV genotyping chip |
CN111208119A (en) * | 2020-02-25 | 2020-05-29 | 北京京东方传感技术有限公司 | Digital microfluidic chemiluminescence detection chip, detection method and detection device |
CN113030070A (en) * | 2021-02-01 | 2021-06-25 | 苏州易莱生物技术有限公司 | Detection device for electrochemical luminescence detection equipment |
CN114279970A (en) * | 2020-04-23 | 2022-04-05 | 深圳市液芯科技有限公司 | Detection system and method for analyzing one or more analytes |
CN114280314A (en) * | 2021-12-13 | 2022-04-05 | 深圳先进技术研究院 | Micro-fluidic chip, analysis system and analysis method for chemiluminescence immunoassay |
CN114544980A (en) * | 2021-06-16 | 2022-05-27 | 南京仁迈生物科技有限公司 | Micro-fluidic blood coagulation detection system |
CN115151346A (en) * | 2020-01-24 | 2022-10-04 | 科锐丽亚生物系统公司 | Automated analyte determination system and kit for use therewith |
TWI838739B (en) * | 2022-04-28 | 2024-04-11 | 瑞霸生技股份有限公司 | Automatic system for continuous measurement of electrochemical information |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100184020A1 (en) * | 2007-12-27 | 2010-07-22 | Lawrence Livermore National Security, Llc. | Chip-Based Sequencing Nucleic Acids |
CN102866193A (en) * | 2012-09-04 | 2013-01-09 | 吴传勇 | Device and method for controlling particles in liquid based on dielectrophoresis |
CN102879453A (en) * | 2012-09-04 | 2013-01-16 | 吴传勇 | Method and component for controlling charged particles in liquid based on electrophoresis |
CN102980996A (en) * | 2012-12-31 | 2013-03-20 | 广州市第一人民医院 | Chemiluminescence immunoassay system, as well as method and application thereof |
US20160274098A1 (en) * | 2015-03-16 | 2016-09-22 | National Chiao Tung University | Magnetic bead-based digital microfluidic immunoanalysis device and method thereof |
CN107843737A (en) * | 2017-12-08 | 2018-03-27 | 均强机械(苏州)有限公司 | Full-automatic micro-fluidic chemiluminescence immunoassay detector |
CN108593944A (en) * | 2018-03-22 | 2018-09-28 | 广州市第人民医院(广州消化疾病中心、广州医科大学附属市人民医院、华南理工大学附属第二医院) | Liquid drop chip immunoassay system and method |
CN209656719U (en) * | 2019-03-07 | 2019-11-19 | 南京迪格诺斯生物技术有限公司 | A kind of chemiluminescence immunoassay system |
-
2019
- 2019-03-07 CN CN201910170361.3A patent/CN109709349B/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100184020A1 (en) * | 2007-12-27 | 2010-07-22 | Lawrence Livermore National Security, Llc. | Chip-Based Sequencing Nucleic Acids |
CN102866193A (en) * | 2012-09-04 | 2013-01-09 | 吴传勇 | Device and method for controlling particles in liquid based on dielectrophoresis |
CN102879453A (en) * | 2012-09-04 | 2013-01-16 | 吴传勇 | Method and component for controlling charged particles in liquid based on electrophoresis |
CN102980996A (en) * | 2012-12-31 | 2013-03-20 | 广州市第一人民医院 | Chemiluminescence immunoassay system, as well as method and application thereof |
US20160274098A1 (en) * | 2015-03-16 | 2016-09-22 | National Chiao Tung University | Magnetic bead-based digital microfluidic immunoanalysis device and method thereof |
CN107843737A (en) * | 2017-12-08 | 2018-03-27 | 均强机械(苏州)有限公司 | Full-automatic micro-fluidic chemiluminescence immunoassay detector |
CN108593944A (en) * | 2018-03-22 | 2018-09-28 | 广州市第人民医院(广州消化疾病中心、广州医科大学附属市人民医院、华南理工大学附属第二医院) | Liquid drop chip immunoassay system and method |
CN209656719U (en) * | 2019-03-07 | 2019-11-19 | 南京迪格诺斯生物技术有限公司 | A kind of chemiluminescence immunoassay system |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110286120A (en) * | 2019-08-15 | 2019-09-27 | 北京农业质量标准与检测技术研究中心 | Flow-type electrochemical luminescence biological detection system |
CN110286120B (en) * | 2019-08-15 | 2024-04-02 | 北京市农林科学院 | Flow type electrochemiluminescence biological detection system |
CN110755699A (en) * | 2019-09-18 | 2020-02-07 | 浙江省北大信息技术高等研究院 | Implantable electroosmotic micropump device |
CN110885907A (en) * | 2019-12-13 | 2020-03-17 | 福建工程学院 | Full-automatic sample adding, hybridizing and detecting method for HPV genotyping chip |
CN115151346A (en) * | 2020-01-24 | 2022-10-04 | 科锐丽亚生物系统公司 | Automated analyte determination system and kit for use therewith |
CN111208119A (en) * | 2020-02-25 | 2020-05-29 | 北京京东方传感技术有限公司 | Digital microfluidic chemiluminescence detection chip, detection method and detection device |
CN114279970A (en) * | 2020-04-23 | 2022-04-05 | 深圳市液芯科技有限公司 | Detection system and method for analyzing one or more analytes |
CN113030070A (en) * | 2021-02-01 | 2021-06-25 | 苏州易莱生物技术有限公司 | Detection device for electrochemical luminescence detection equipment |
CN114544980A (en) * | 2021-06-16 | 2022-05-27 | 南京仁迈生物科技有限公司 | Micro-fluidic blood coagulation detection system |
CN114280314A (en) * | 2021-12-13 | 2022-04-05 | 深圳先进技术研究院 | Micro-fluidic chip, analysis system and analysis method for chemiluminescence immunoassay |
CN114280314B (en) * | 2021-12-13 | 2023-09-19 | 深圳先进技术研究院 | Microfluidic chip, analysis system and analysis method for chemiluminescence immunoassay |
TWI838739B (en) * | 2022-04-28 | 2024-04-11 | 瑞霸生技股份有限公司 | Automatic system for continuous measurement of electrochemical information |
Also Published As
Publication number | Publication date |
---|---|
CN109709349B (en) | 2024-02-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109709349A (en) | A kind of chemiluminescence immunoassay system | |
CN108535239B (en) | Micro-fluidic chip and detection system based on micro-droplets | |
US7258837B2 (en) | Microfluidic device and surface decoration process for solid phase affinity binding assays | |
US9683994B2 (en) | High throughput mobility shift | |
US7138269B2 (en) | Microflow system for particle separation and analysis | |
CN101576557B (en) | Integrated micro-fluidic chip system | |
JP6714603B2 (en) | Sample processing chip, sample processing apparatus, and sample processing method | |
CN102472739A (en) | Centrifugal micro-fluidic device and method for detecting analytes from liquid specimen | |
CN103223357A (en) | Microfluidic device and control method thereof | |
US20030027225A1 (en) | Microfluidic devices and systems for separating components of a mixture | |
US20100233822A1 (en) | Device for analyzing fluids | |
US20060246575A1 (en) | Microfluidic rare cell detection device | |
CA2353998A1 (en) | Method and apparatus for continuous liquid flow in microscale channels using pressure injection, wicking, and electrokinetic injection | |
CN102580644A (en) | Microfluidic device and analyte detection method using the same | |
WO2005070533A1 (en) | System for characterising a fluid, microfluidic device for characterising or analysing concentrations components, a method of characterising or analysing such concentrations and a measurement | |
GB2392977A (en) | A fluidic dielectrophoretic system and method for analysing biomolecules | |
WO2001014865A1 (en) | Dilutions in high throughput systems with a single vacuum source | |
CN103223323B (en) | Magnetic separation technology and micro-fluid technology based rapid detection micro-fluid reactor, and making method and detection method thereof | |
CN209656719U (en) | A kind of chemiluminescence immunoassay system | |
WO2008036083A1 (en) | Microfluidic flow cytometer and applications of same | |
Nelson | Design principles for microfluidic biomedical diagnostics in space | |
CN111632631B (en) | Microfluidic substrate, microfluidic device, and fluid driving method | |
CN212134464U (en) | Light-activated chemiluminescence micro-fluidic device and instant detection system | |
Demchenko et al. | The sensing devices | |
JP2023524069A (en) | System and method for sample analysis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 210000 Hongfeng Science and Technology Park, Nanjing Economic and Technological Development Zone, Jiangsu Province Applicant after: Nanjing renmai Biotechnology Co.,Ltd. Address before: 210000 Hongfeng Science and Technology Park, Nanjing Economic and Technological Development Zone, Jiangsu Province Applicant before: NANJING DGNS BIOTECH CO.,LTD. |
|
CB02 | Change of applicant information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |