CN209131768U - A kind of liquid quantifying device - Google Patents

A kind of liquid quantifying device Download PDF

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Publication number
CN209131768U
CN209131768U CN201820619456.XU CN201820619456U CN209131768U CN 209131768 U CN209131768 U CN 209131768U CN 201820619456 U CN201820619456 U CN 201820619456U CN 209131768 U CN209131768 U CN 209131768U
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liquid
area
quantitative
liquid quantitative
entrance
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蒙玄
万惠芳
胡海升
李文美
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Guangzhou Wondfo Biotech Co Ltd
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Guangzhou Wondfo Biotech Co Ltd
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Abstract

The utility model discloses a kind of liquid quantifying devices comprising matrix and the liquid quantitative area in described matrix;The liquid quantitative area has predetermined volume, and the both ends in the liquid quantitative area are respectively equipped with liquid quantitative entrance and liquid quantitative outlet, liquid flows into the liquid quantitative area from liquid quantitative entrance, exports full of the liquid quantitative is reached behind the liquid quantitative area;The corresponding position of the liquid quantitative outlet is equipped with Liquid identification device, and the Liquid identification device reaches the liquid of the liquid quantitative outlet for identification.The application that the invention also discloses liquid quantifying devices in micro-fluidic chip.Quantitative and detection accuracy can be improved using the utility model.

Description

A kind of liquid quantifying device
Technical field
The utility model relates to fluid quantitative field more particularly to a kind of liquid quantifying devices.
Background technique
In-vitro diagnosis (In Vitro Diagnosis, IVD) refers to taking-up sample (blood, body fluid, the tissue from human body Deng) test and analyze to being diagnosed to disease, need corresponding instrument and reagent in detection process, and these instruments and Reagent just constitutes extracorporeal diagnostic system.The system of in-vitro diagnosis is roughly divided into two kinds;One is be with inspection center laboratory Represent, it have system modular, automation, the carry out Sample of pipeline system, thus also have high throughput, high efficiency, The advantage of high sensitive, but whole system also has somewhat expensive, shared volume is big, the defect for needing professional to operate, it It is mainly used in large hospital.Another be with detect immediately (point-of-care testing, POCT) be representative, it System have it is integrated, miniaturization, carry out Sample whenever and wherever possible, thus also have price material benefit, it is easy to operate, as a result Report timely advantage, but its test result compares that there is also sensitivity, the not high disadvantages of stability with central laboratory.
For POCT, has both at home and abroad and microflow control technique is applied in the product of in-vitro diagnosis.It is micro-fluidic It (microfluidics) is a cross discipline for carrying out control operation to microfluid on one piece of chip with microchannel, It is related to the fields such as biology, chemistry, fluid physics, electronics, optics, mechanical engineering.Micro fluidic device is commonly known as micro-fluidic Chip, also referred to as chip lab (Lab on a Chip).Usually biology, chemical, medical analysis process sample system The basic operations such as standby, reaction, separation, detection are concentrated on one chip, and a system function is completed.Existing micro-fluidic chip Mainly based on qualitative detection, the micro-fluidic chip for being able to achieve quantitative detection is less, and structure is complicated;Especially it is directed to Apparatus for metering liquid, some using specific volume bag container, although such D-M (Determiner-Measure) construction is simple, bag container surface pole Liquid hanging bag phenomenon easily occur, (when extruding liquid from bag container, partially liq extension is stayed in bag, not can guarantee liquid All extrude), and the deflection that bag container is squeezed every time is all different, so remaining in the amount of liquid in bag container every time It is inconsistent, and then the amount of liquid that liquid is extruded is different, when in particular for gobbet, the error of bag container is more Greatly, relative to micro-fluidic chip, what is needed is all tens microlitres of amount, so the quantitative accurate degree of bag container is unable to reach and wants It asks, dosing accuracy is poor, to influence testing result, while bag container needs to be built into chip, increases the life of chip Produce difficulty.
Utility model content
On the one hand, the utility model provides a kind of liquid quantifying device, the liquid quantifying device structure of the utility model Simply, quantitative precision is high.
A kind of the technical solution adopted in the utility model are as follows: liquid quantifying device comprising matrix and be set to the base Liquid quantitative area on body;
The liquid quantitative area has predetermined volume, and the both ends in the liquid quantitative area are respectively equipped with liquid quantitative entrance It is exported with liquid quantitative, liquid flows into the liquid quantitative area from liquid quantitative entrance, full of reaching behind the liquid quantitative area The liquid quantitative outlet;
The corresponding position of the liquid quantitative outlet is equipped with Liquid identification device, and the Liquid identification device is for identification Reach the liquid of the liquid quantitative outlet.
The Liquid identification device is set to the outside of described matrix in one of the embodiments,.An implementation wherein In example, the Liquid identification device includes light source generation module and photoelectric sensor;The light source generation module, the liquid are fixed Measure mouth, the perpendicular line of the photoelectric sensor is successively laid.
The liquid quantitative inlet also is provided with Liquid identification device in one of the embodiments,.
The Liquid identification device includes light source generation module and photoelectric sensor in one of the embodiments,;It is described The outside of described matrix is arranged in Liquid identification device;
Liquid identification device set on the liquid quantitative exit is according to light source generation module, liquid quantitative outlet, light The perpendicular line of electric inductor is successively laid;
Liquid identification device set on the liquid quantitative inlet is according to light source generation module, liquid quantitative entrance, light The perpendicular line of electric inductor is successively laid.
Described matrix includes top plate and bottom plate in one of the embodiments, and the top plate and bottom plate stacking connect; The junction of the top plate and the bottom plate is arranged in the liquid quantitative area;
Light source generation module setting set on the Liquid identification device in the liquid quantitative exit is determined with the liquid Measure the surface of the corresponding position of the corresponding top plate of mouth, photoelectric sensor setting with liquid quantitative outlet pair The underface of the corresponding position for the bottom plate answered;
Light source generation module setting set on the Liquid identification device of the liquid quantitative inlet is determined with the liquid Measure the surface of the corresponding position of the corresponding top plate of entrance, photoelectric sensor setting with the liquid quantitative entrance pair The underface of the corresponding position for the bottom plate answered.
The liquid quantitative area is hexagonal structure in one of the embodiments,.
The width of the liquid quantitative entrance in the liquid quantitative area is 0.3-3mm in one of the embodiments, is highly 0.3-3mm;The width of the liquid quantitative outlet in the liquid quantitative area is 0.3-3mm, is highly 0.3-3mm.
The surface for stating liquid quantitative area in one of the embodiments, is the table formed after hydrophilic surface is modified Face;The width of the liquid quantitative entrance in the liquid quantitative area is 0.3-5mm, is highly 0.3-3mm;The liquid quantitative area The width of liquid quantitative outlet is 0.3-5mm, is highly 0.3-3mm.
The surface in the liquid quantitative area is the table formed after hydrophobic surface is modified in one of the embodiments, The width in face, the liquid quantitative entrance in the liquid quantitative area is 0.3-2mm, is highly 0.3-3mm;The liquid quantitative area The width of liquid quantitative outlet is 0.3-2mm, is highly 0.3-3mm.
Described matrix includes top plate and bottom plate in one of the embodiments, and the top plate and bottom plate stacking connect; The junction of the top plate and the bottom plate is arranged in the liquid quantitative area.
In one of the embodiments, the top plate be equipped with groove, the bottom plate be smooth plate, the groove with The bottom plate cooperatively forms the liquid quantitative area.
Fluid passage is additionally provided in described matrix in one of the embodiments, the fluid passage and the liquid are fixed Measure entrance connection.
Air subchannel and air intake are additionally provided in described matrix in one of the embodiments, the air branch is logical The one end in road is connected to the fluid passage, and the other end of the air subchannel is connected to the air intake, the air Liquid quantitative entrance of the connectivity part of subchannel and the fluid passage adjacent to the liquid quantitative area.
On the other hand, the utility model additionally provides above-described liquid quantifying device answering in micro-fluidic chip With.
Compared with the existing technology, the utility model has the following beneficial effects:
The liquid quantifying device of the utility model combines the liquid in liquid quantitative exit by specific liquid quantitative area Identification device realizes quantifying for liquid, and structure is simple and novel, and quantitative precision is high;By being further arranged positioned at liquid quantitative The Liquid identification device of inlet can be convenient for being monitored the flowing of liquid in matrix and bubble that may be present, controlling, into One step improves quantitative precision.
When the liquid quantifying device of the utility model is applied on micro-fluidic chip, the accuracy of detection can be improved, together When the outside of chip may be disposed at due to Liquid identification device, can facilitating chip producting process difficulty.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of liquid quantifying device provided by the utility model;
Fig. 2 is the schematic cross-section of Liquid identification device provided by the utility model;
Fig. 3 is a kind of structural schematic diagram of embodiment of micro-fluidic chip provided by the utility model;
Fig. 4 is a kind of arrangement structure for sensor figure of embodiment of micro-fluidic chip provided by the utility model;
Fig. 5 is the schematic cross-section of magnet setting position when micro-fluidic chip provided by the utility model uses;
Fig. 6 is a kind of structural schematic diagram of embodiment of liquid driving device provided by the utility model;
Wherein, 1, top plate;2, injection port, 3, Whole Blood Filtration area;4, sample amounts area;5, enzyme mark primary antibody embeds area;6, One mixes channel;7, magnetic mark secondary antibody embeds area;8, second channel is mixed;9, chemiluminescence detection area;10, dilution entrance;11, Substrate luminescent solution entrance;12, filter washing water inlet;13, liquid driven power entrance;14, air intake;15, gasket;16, it dilutes Liquid subchannel;17, substrate luminescent solution subchannel;18, cleaning solution subchannel;19, plunger pump;20, bottom plate;21, dilution stores Pond;22, substrate luminescent solution storage pool;23, cleaning solution storage pool;24, waste liquid pool;25a/25b, magnet;26, magnetic bead;27, air Subchannel;28, light source generation module;29, photoelectric sensor;191, the inlet of plunger pump;192, the liquid outlet of plunger pump; 193, plunger;194, pump chamber.
Specific embodiment
The following will be combined with the drawings in the embodiments of the present invention, carries out the technical scheme in the embodiment of the utility model Clearly and completely describe, it is clear that the described embodiments are only a part of the embodiments of the utility model, rather than whole Embodiment.Based on the embodiments of the present invention, those of ordinary skill in the art are without creative efforts Every other embodiment obtained, fall within the protection scope of the utility model.
Embodiment 1
Referring to FIG. 1, present embodiments providing a kind of liquid quantifying device comprising matrix and the liquid on matrix Body quantification area 100.
Liquid quantitative area 100 has predetermined volume, and the both ends in liquid quantitative area are respectively equipped with 101 He of liquid quantitative entrance Liquid quantitative outlet 102, liquid arrives behind 101 influent quantification area 100 of liquid quantitative entrance, hydraulically full quantification area 100 Up to liquid quantitative outlet 102.
The corresponding position of liquid quantitative outlet 102 is equipped with Liquid identification device, and Liquid identification device reaches for identification The liquid of liquid quantitative outlet 102.
In above technical scheme, since liquid quantitative area 100 has predetermined volume, and it allows liquid from liquid quantitative 101 influent quantification area 100 of entrance reaches liquid quantitative outlet 102 behind hydraulically full quantification area 100, when liquid reaches liquid When body is quantitatively exported at 102, Liquid identification device can provide liquid arriving signal, and indicating liquid fills liquid quantitative area 100 It is full, liquid is controlled at this time and stops entering liquid quantitative area 100, is realized liquid quantifying in liquid quantitative area 100, is quantitatively obtained Liquid volume be liquid quantitative area 100 volume.
It should be noted that this is not restricted for the structure of Liquid identification device, it can identify that the device of liquid can be made For the sensing of liquid disclosed in the Liquid identification device of the utility model, such as the patent application of Publication No. " 105214744A " Device can be used as the Liquid identification device of the utility model, but this liquid sensing device structure is complex, and conductive pin needs It is built into chip interior, and conductive pin is contacted with reaction liquid, will affect experimental result in any case.Preferably, Liquid identification device is set to the outside of matrix, such as is detected by Optical Implementation, and contactless mode will not interfere inspection It surveys, also facilitates the processing and fabricating of matrix chip.
As shown in Figure 2, it is preferable that Liquid identification device includes light source generation module 28 and photoelectric sensor 29;Liquid is known The outside of matrix is arranged in other device;
Liquid identification device at liquid quantitative outlet 102 is according to light source generation module 28, liquid quantitative outlet 102 It is successively laid with the perpendicular line of photoelectric sensor 29.Using optical sensing come to Liquid identification, quantitative and control, relative to conduction The way of contact of formula, the intervention this method reduces metal to reaction system in chip can be improved detection efficiency, and then improve and determine The accuracy of amount, while such Liquid identification device can be set to outside micro-fluidic chip, convenient for being fixed in instrument, without It is arranged on chip, reduces the difficulty of processing of chip.In use, only light source generation module and photoelectric sensor need to be directed at liquid Body recognition site is placed.
Light source generation module 28 is the module for being capable of providing light source, can be LED, halogen lamp.Under the irradiation of light source, by In gas, liquid to the transmissivity and refractive index difference of light, the light intensity for being irradiated to photoelectric sensor is different, and photoelectric sensor is just Gas and liquid can be identified, to distinguish whether liquid arrives the point of induction.When liquid flow to liquid quantitative entrance or liquid When quantitative liquid-discharging mouth, Liquid identification device can be identified quickly, so that controlling liquid stops flow into liquid quantitative area.
Optionally, Liquid identification device also is provided at liquid quantitative entrance 101.The setting of Liquid identification device can convenient for pair The flowing of liquid and issuable bubble are monitored, control in matrix, to can further improve quantitative accuracy.It is excellent Selection of land, the Liquid identification device at liquid quantitative entrance 101 are identical as the Liquid identification device at liquid quantitative outlet 102.? In one preferred embodiment, the Liquid identification device at liquid quantitative entrance 101 is set to the outside of matrix comprising light source The outside of matrix is arranged in generation module and photoelectric sensor, light source generation module and photoelectric sensor;Enter set on liquid quantitative Liquid identification device at mouth 101 is according to light source generation module 28, liquid quantitative entrance 101 and the perpendicular line of photoelectric sensor 29 Successively lay.
Liquid quantitative area 100 can be shaped by various ways such as laser processing, model injection moldings in intrinsic silicon, Specific groove shapes can be processed on top plate 1 or bottom plate 20, then by being set as the top plate 1 and bottom plate 20 of separate type Mutually it is packaged together;Since former processing method is relatively complicated, in a preferred embodiment, matrix includes top plate 1 With bottom plate 20;Top plate 1 and the stacking of bottom plate 20 connect;The junction of 1 top plate and bottom plate 20 is arranged in liquid quantitative area 100.Accordingly Ground, the light source generation module 28 of the Liquid identification device at liquid quantitative outlet 102 is arranged to be exported with liquid quantitative The surface of the corresponding position of 102 corresponding top plates 1, the setting of photoelectric sensor 29 is corresponding with liquid quantitative outlet 102 The underface of the corresponding position of bottom plate 20;The light source generation module of Liquid identification device at liquid quantitative entrance 101 is set The surface in the corresponding position of top plate corresponding with liquid quantitative entrance 101 is set, photoelectric sensor setting is fixed with liquid Measure the underface of the corresponding position of the corresponding bottom plate of entrance 101.
In a preferred embodiment, top plate 1 is equipped with groove, and bottom plate 20 is smooth plate, groove and bottom plate 20 cooperatively form liquid quantitative area 100;The preparation of such liquid quantifying device is got up more convenient, reduces production technology hardly possible Degree only need to process required specific structure on top plate, improve production efficiency.
The liquid quantitative area of the utility model can be realized " inlet influent of the liquid that need to be quantified from liquid quantitative area Body quantification area reaches liquid outlet behind hydraulically full quantification area ", shape and structure can be selected as needed, this is practical It is novel to be imposed any restrictions not to this, such as it can be pipe shape, polygonal shape etc..In one embodiment, the liquid Quantification area is the chamber of hexagonal structure.
Optionally, the width of the liquid quantitative entrance 101 in liquid quantitative area is 0.3-3mm (preferably 0.8-1.5mm), Height is 0.3-3mm;The width of the liquid quantitative outlet 102 in liquid quantitative area is 0.3-3mm (preferably 0.8-1.5mm), high Degree is 0.3-3mm.Liquid quantitative throat width is wide or narrow, excessive height or it is too low be unfavorable for quantitative progress, work as liquid When body quantifies wide throat width or excessive height, be easy to cause liquid can not hydraulically full quantification area flow to its liquid quantitative Outlet cannot achieve accurate liquid quantitative in this way, and when liquid quantitative throat width is narrow or height is too low, then need phase Length should be increased to meet the requirement of volume, may result in the increase of chip length and the increase of chip volume in this way.
Optionally, the surface in liquid quantitative area 100 is the surface formed after hydrophilic surface is modified;Liquid quantitative area Liquid quantitative entrance 101 width be 0.3-5mm, be highly 0.3-3mm;The liquid quantitative outlet 102 in liquid quantitative area Width is 0.3-5mm, is highly 0.3-3mm.Hydrophilic surface modification includes but is not limited to plasma plus hydroxyl, carboxyl modified. After the surface in liquid quantitative area carries out Hydrophilic modification, it is more advantageous to the filling of liquid in the cavity, appropriate can be increased at this time The width that liquid quantitative entrance, the liquid quantitative in liquid quantitative area export, so as to reduce the length in liquid quantitative area and chip.
Optionally, the surface in liquid quantitative area 100 is the surface formed after hydrophobic surface is modified, liquid quantitative area Liquid quantitative entrance 101 width be 0.3-2mm, be highly 0.3-3mm;The liquid quantitative outlet 102 in liquid quantitative area Width is 0.3-2mm, is highly 0.3-3mm.The surface in liquid quantitative area can prevent liquid from hanging after hydrophobic surface is modified Wall, and can guarantee and reach liquid quantitative outlet after liquid is full of in liquid quantitative area.
Optionally, fluid passage 103 is additionally provided on matrix, fluid passage 103 is connected to liquid quantitative entrance 101.
Further, air subchannel 104 and air intake 105, one end of air subchannel 104 are additionally provided on matrix It is connected to fluid passage 103, the other end of air subchannel 104 is connected to air intake 105, air subchannel 104 and liquid Liquid quantitative entrance 101 of the connectivity part in channel 103 adjacent to liquid quantitative area.In one embodiment, " neighbouring " reason herein Solution for " the distance between the liquid quantitative entrance 101 in connectivity part and liquid quantitative area be 0.5~10mm (preferably 0.5~ 2mm)".In use, the air pipeline of air intake and matrix outer can be connected to on-off by valve, with control air into Enter intrinsic silicon.Liquid is through in liquid quantitative entrance influent quantification area, when liquid flow to the liquid quantitative in liquid quantitative area When exit, i.e., hydraulically full quantification area, the Liquid identification device for being now placed in liquid quantitative outlet issues liquid arriving signal, It controls air intake to open, the driving force as needed for the flowing of air in air subchannel is small, and driving needed for the flowing of liquid Power is bigger, therefore liquid rests on air subchannel and the connectivity part of fluid passage does not continue to influent quantification area The liquid of specific quantity after being separated.
The liquid quantifying device of the present embodiment combines the liquid in liquid quantitative exit to know by specific liquid quantitative area Other device realizes quantifying for liquid, and structure is simple and novel, and quantitative precision is high.
When the liquid quantifying device of the present embodiment is applied on micro-fluidic chip, the accuracy of detection can be improved, simultaneously Since Liquid identification device may be disposed at the outside of chip, can facilitating chip producting process difficulty.
Embodiment 2
Referring to figure 2.~Fig. 6 present embodiments provides the liquid quantifying device in embodiment 1 on micro-fluidic chip Using.In the present embodiment, micro-fluidic chip is chemiluminescence micro-fluidic chip.
The chemiluminescence micro-fluidic chip of the present embodiment, including chip body and the sample introduction being arranged in chip body Mouth 2, liquid driven power entrance 13, substrate luminescent solution entrance 11, filter washing water inlet 12, substrate luminescent solution subchannel 17, cleaning solution Subchannel 18, main fluid passageway and multiple functional areas;It is specifically described below.
In the present embodiment, main fluid passageway is connected to multiple functional areas, to guide flowing of the fluid between functional areas.
Functional areas include the enzyme mark primary antibody embedding area 5 being sequentially communicated by main fluid passageway, magnetic mark secondary antibody embedding 7 and of area Chemiluminescence detection area 9.
Wherein, enzyme mark primary antibody embedding area 5 is embedded with enzyme mark primary antibody;Magnetic mark secondary antibody embedding area 7 is embedded with magnetic mark secondary antibody;Magnetic mark It is liquid quantitative area that secondary antibody, which embeds area 7,;Liquid quantitative area be used for quantitative liquid, to quantitative liquid (such as substrate luminescent solution) into After entering liquid quantitative area, quantitative (obtaining desired amount of liquid) can be realized in liquid quantitative area, with quantitative liquid Sample or the reaction of other reaction reagents, to realize quantitative detection.
In the present embodiment, liquid quantitative area has scheduled volume, and is provided at the liquid outlet in liquid quantitative area Liquid identification device, the liquid that need to be quantified is behind the inlet influent quantification area in liquid quantitative area, hydraulically full quantification area Reach liquid outlet.When liquid reaches at liquid outlet, Liquid identification device can provide liquid arriving signal, and indicating liquid is by liquid Body quantification area is full of, and is controlled liquid driving device at this time and is stopped driving liquid, liquid can be realized and determine in liquid quantitative area Amount.Chemiluminescence micro-fluidic chip realizes quantifying for liquid in conjunction with liquid driving device by specific liquid quantitative area, can Improve quantitative accuracy.
In the present embodiment, chemiluminescence detection area 9 is for accommodating chemiluminescence reaction product, with external detection device In conjunction with completion detection process.
Injection port 2 is connected to main fluid passageway respectively with liquid driven power entrance 13, and driving force entrance 13 is for connecting liquid Body drive is to drive liquid inflow or downstream area;Injection port 2 is for fluid sample to be introduced into main fluid passageway, liquid Body sample enters each functional areas through main fluid passageway.
In the present embodiment, one end of substrate luminescent solution subchannel 17 is connected to substrate luminescent solution entrance 11, the other end It is connected to the inlet in magnetic mark secondary antibody embedding area 7, substrate luminescent solution is through substrate luminescent solution entrance 11, substrate luminescent solution subchannel 17 It is quantified into magnetic mark secondary antibody embedding area 7.
One end of cleaning solution subchannel 18 is connected to filter washing water inlet 12, the other end and magnetic mark secondary antibody embedding area 7 into The connection of liquid mouth, the cleaned liquid entrance 12 of cleaning solution, cleaning solution subchannel 18 enter magnetic mark secondary antibody embedding area 7 and carry out magnetic bead cleaning.
The micro-fluidic chip of the present embodiment is in use, substrate luminescent solution entrance 11, filter washing water inlet 12 are sent out with substrate respectively Light liquid storage pool 22, cleaning solution storage pool 23 can be connected to on-off by valve V2, V3, substrate luminescent solution storage pool 22, cleaning The opening being connected to outside air is respectively equipped on liquid storage pool 23;Liquid driving device is mounted on liquid driven power entrance 13 Place, flows to liquid in driving chip;The outside in magnetic mark secondary antibody embedding area 7 is fixed with magnet (such as magnet 25a, 25b), with Just magnetic bead 26 is fixed.It is liquid quantitative area that magnetic mark secondary antibody, which embeds area, can be used for quantifying substances luminescent solution, optionally, can also be into One step is used for quantitative cleaning solution.
One working method of the micro-fluidic chip of the present embodiment is as follows: the fluid sample of predetermined amount is (such as through diluted Serum or blood plasma afterwards) under the action of liquid driving device at injection port 2 through main fluid passageway flow to enzyme mark primary antibody embedding Area 5, with the enzyme mark primary antibody hybrid reaction wherein embedded, reaction solution reaches magnetic mark secondary antibody and embeds area 7 thereafter, with the magnetic wherein embedded Mark secondary antibody continuess to mix reaction, and the reactant of double antibodies sandwich structure is formed on magnetic bead, and magnetic bead is adsorbed by magnet, and reactant is in magnetic Under the action of pearl stablize magnetic mark secondary antibody embedding area 7 in, and remaining reaction solution under the action of liquid driving device through liquid Chip is discharged in driving force entrance 13;Then, the air inflow end mouth (such as sample inlet) on chip is closed, cleaning solution storage is opened Valve V3 between pond 23 and filter washing water inlet 12, cleaning solution under the action of liquid driving device cleaned liquid subchannel 18 into Enter magnetic mark secondary antibody embedding area 7 to clean to magnetic bead therein, when magnetic mark secondary antibody embedding area 7 completes to quantify cleaning solution When, the valve V3 between cleaning solution storage pool 23 and filter washing water inlet 12 can be closed, air inflow end mouth is opened, after cleaning Chip is discharged through liquid driven power entrance 13 under the action of liquid driving device in liquid can be repeatedly in order to guarantee cleaning effect (magnetic bead cleaning way is not limited to mode described herein, can also be for example, by the moving magnet in cleaning solution for several times for cleaning Mode realizes the cleaning of magnetic bead);The air inflow end mouth (such as sample inlet) being then switched off on chip opens the storage of substrate luminescent solution The valve V2 between pond 22 and substrate luminescent solution entrance 11 is deposited, substrate luminescent solution is sent out under the action of liquid driving device through substrate Light liquid subchannel 17 enter magnetic mark secondary antibody embed area 7, when magnetic mark secondary antibody embedding area 7 complete to substrate luminescent solution it is quantitative when, close The valve V2 between substrate luminescent solution storage pool 22 and substrate luminescent solution entrance 11 is closed, liquid driving device stops driving effect, Substrate luminescent solution is no longer flow into magnetic mark secondary antibody embedding area 7, opens the air inflow end mouth (such as sample inlet) on chip, magnetic mark two The reactant of substrate luminescent solution and magnetic capture after resisting quantitatively carries out luminescence-producing reaction, removes magnet, the embedding of magnetic mark secondary antibody later Reaction solution in area 7 flows into chemiluminescence detection area 9 under the action of liquid driving device and is detected.
Above-mentioned chemiluminescence microfluidic chip structure is compact, such as magnetic mark secondary antibody embedding area is applied not only to embedding magnetic mark two It is anti-, it can also be used in quantifying substances luminescent solution as liquid quantitative area, and liquid quantitative area need not be separately set again, magnetic mark secondary antibody Embedding Qu Haike is further used as the area cleaned for magnetic bead, and magnetic bead cleaning area need not separately be arranged again, and core is greatly saved The volume of piece;Meanwhile reagent storage pool (such as substrate luminescent solution storage pool, cleaning solution storage pool) is external to chip, relatively It is plated in chip in prior art reagent, reduces the manufacture craft difficulty of chip, improve the accuracy of detection.
It should be noted that main fluid passageway and multiple functional areas can be more by laser processing, model injection molding etc. Kind of mode shapes inside chip body, can also be processed on top plate or bottom plate by being set as the top plate and bottom plate of separate type Then specific shape out is mutually packaged together;Since former processing method is relatively complicated, in a preferred embodiment In, chip body includes top plate 1 and bottom plate 20;Top plate 1 and the stacking of bottom plate 20 connect;The junction of top plate 1 and bottom plate 20 is arranged There are main fluid passageway and multiple functional areas;It is highly preferred that bottom plate 20 be smooth plate, top plate 20 be arranged micropore, microchannel or Micro-nano chamber with bottom plate cooperatively form injection port 2, liquid driven power entrance 13, substrate luminescent solution entrance 11, filter washing water inlet 12, Substrate luminescent solution subchannel 17, cleaning solution subchannel 18, main fluid passageway or multiple functional areas, such micro-fluidic chip preparation Get up more convenient, further reduced producting process difficulty, only required specific structure need to be processed on top plate, into one Step improves production efficiency.In one embodiment, bottom plate 20 be smooth plate, top plate 1 be equipped with multiple microchannels with Bottom plate 20, which combines, forms main fluid passageway, and top plate 1 is equipped with multiple microcavitys to form multiple functional areas to be combined with bottom plate 20, pushes up Plate 1 is equipped with the combination of multiple Kong Yiyu bottom plates 20 and forms injection port 2, liquid driven power entrance 13,11 and of substrate luminescent solution entrance Filter washing water inlet 12;For the ease of sample introduction, the size of injection port 2 is typically larger than the size of other entrances.
Therefore, the chip body of above-mentioned chemiluminescence micro-fluidic chip may include the top plate and bottom plate being stacked, and need On the settable top plate of the structure completed the process, bottom plate is only smooth plate, can further decrease the production of chip in this way Technology difficulty improves production efficiency.
Optionally, Liquid identification device is also equipped at the inlet in liquid quantitative area.The setting of this Liquid identification device Two kinds of quantitative liquids can be can also be achieved convenient for being monitored, controlling to the flowing of liquid in chip and bubble that may be present Between mixing.
Further, enzyme mark primary antibody embedding area 5 is also liquid quantitative area, is additionally provided with 10 He of dilution entrance in chip body Dilution subchannel 16;One end of dilution subchannel 16 is connected to dilution entrance 10, and the other end and enzyme mark primary antibody embed area 5 Inlet connection, sample diluting liquid through dilution entrance, dilution subchannel enter enzyme mark primary antibody embedding area 5 quantified. Further, it is respectively arranged with Liquid identification device at the inlet and liquid outlet in enzyme mark primary antibody embedding area 5, the liquid that need to be quantified Body flows into enzyme mark primary antibody from its inlet and embeds area 5, reaches liquid outlet after embedding area 5 full of enzyme mark primary antibody.Sample diluting liquid is not Only can diluent liquid sample (such as serum, blood plasma), its concentration and viscosity are reduced, wherein the substance contained can also reduce liquid The background values of body sample, so that detection is more accurate, while sample diluting liquid can preferably redissolve enzyme mark primary antibody;In this technology In scheme, enzyme mark primary antibody embedding area can be used for quantifying sample diluting liquid, without realizing determining for sample diluting liquid in chip exterior Amount, quantitative sample diluting liquid can embed area in enzyme mark primary antibody and be mixed with quantitative fluid sample, can save manpower, operate It is more convenient.In use, dilution entrance 10 can be connect to on-off with dilution storage pool 21 by valve V1, dilution storage It deposits pond 21 and is equipped with the opening being connected to outside air;Fluid sample (serum or blood such as after diluted of predetermined amount Slurry) it flow to the inlet in enzyme mark primary antibody embedding area 5 through main fluid passageway at injection port 2 under the action of liquid driving device Place closes the air intake (such as sample inlet) on chip, opens the valve between dilution storage pool 21 and dilution entrance 10 Door V1, sample diluting liquid enter enzyme mark primary antibody through dilution subchannel 16 under the action of liquid driving device and embed area 5, when Its full of enzyme mark primary antibody embed area 5, reach enzyme mark primary antibody embedding area 5 liquid outlet at when, close dilution storage pool 21 with it is dilute The valve V1 between liquid entrance 10 is released, is opened air inflow end mouth (such as sample inlet), fluid sample and sample diluting liquid Continue to flow under the suction function of liquid driving device, and can be in the positive pressure of liquid driving device, negative pressure alternating action in master Fluid channel, the embedding of enzyme mark primary antibody realize mixing in area 5, can also realize preferably mixing by the hybrid channel of setting certainly.
Optionally, chemiluminescence detection area 9 has scheduled volume, and sets at the liquid outlet in chemiluminescence detection area 9 It is equipped with Liquid identification device, liquid to be detected flows into chemiluminescence detection area 9 through the inlet in chemiluminescence detection area 9, fills Liquid outlet is reached behind full chemiluminescence detection area 9, the volume in chemiluminescence detection area 9 is less than or equal to magnetic mark secondary antibody embedding area 7 Volume.Reaction solution after substrate luminescent solution is reacted with the reactant of magnetic capture reaches the liquid out in chemiluminescence detection area When at mouthful, Liquid identification device issues signal, and liquid driving device controls reaction solution and stops flowing, can be detected at this time. Further, Liquid identification site, the volume etc. in chemiluminescence detection area 9 also are provided at the inlet in chemiluminescence detection area 9 Volume in magnetic mark secondary antibody embedding area 7.
Optionally, for the ease of the mixing between fluid sample, reagent (sample diluting liquid, substrate luminescent solution etc.), mainstream Body channel includes that the first mixing channel 6 and second mix channel 8;First, which mixes channel 6, is set to enzyme mark primary antibody embedding area 5 and magnetic mark Secondary antibody embeds between area 7;Second, which mixes channel 8, is set between magnetic mark secondary antibody embedding area 7 and chemiluminescence detection area 9.
Optionally, injection port 2 and liquid driven power entrance 13 are separately positioned on the both ends of main fluid passageway.
As shown in figure 4, optionally, for the ease of fixed magnetic bead, chip body position corresponding with magnetic mark secondary antibody embedding area 7 The place of setting is provided with the fixed site of magnet;Further, it is carried out since the cleaning of magnetic bead can embed area 7 in magnetic mark secondary antibody, in order to more Realize that magnetic bead cleans well, the embedding of magnetic mark secondary antibody respectively lays one for phase magnet 25a, the magnetic of 25b above and below area 7 Ferropexy site, two magnet 25a, the diagonally opposing corner that 25b corresponds to magnetic mark secondary antibody embedding area 7 are laid.
Optionally, functional areas further include sample amounts area 4, and sample amounts area 4 is also liquid quantitative area, fluid sample pass through into Sample mouth flows into sample amounts area 4 and is quantified;Sample amounts area 4 is located at the upstream in enzyme mark primary antibody embedding area 5;Micro-fluidic chip On the air subchannel 27 that is additionally provided with air intake 14 and communicates therewith, one end of air subchannel 27 and air intake 14 connect Logical, the main fluid passageway between the other end and sample amounts area 4 and injection port 2 is connected to, the other end of air subchannel 27 and master The connectivity part of fluid channel is adjacent to sample amounts area 4." neighbouring " usually can be regarded as the " feed liquor apart from sample amounts area 4 herein 0.5~10mm of mouth (preferably 0.5~2mm) ".By being provided with sample amounts area, quantifying for fluid sample can be convenient for, without It is separately quantitative outside chip so that chip use it is more convenient.Further, liquid is provided at the liquid outlet in sample amounts area 4 Body identification device, need to liquid quantitatively flow into sample amounts area 4 from its inlet, full of reaching liquid outlet behind sample amounts area 4. Further, Liquid identification device is also equipped at the inlet in sample amounts area 4.
Micro-fluidic chip in use, air intake and the air pipeline of chip exterior can be connected to on-off by valve, Enter chip interior to control air.Fluid sample under the action of liquid driving device through injection port from sample amounts areas into Liquid mouth flows into sample amounts area, when at the liquid outlet that fluid sample flow to sample amounts area, that is, is full of sample amounts area, this When the Liquid identification device that is positioned on the Liquid identification site of liquid outlet issue indication signal, control air intake is opened, The driving force as needed for the flowing of air in air subchannel is small, and driving force needed for the flowing of fluid sample is bigger, therefore liquid Body sample rests on air subchannel and the connectivity part of main fluid passageway does not continue to flow into sample amounts area, and liquid can be completed Sample quantifying in sample amounts area.Fluid sample after quantitative can continue to flow to enzyme mark under the action of liquid driving device Primary antibody embeds area.
Optionally, fluid sample is whole blood, and Whole Blood Filtration area 3, whole blood mistake are equipped between injection port 7 and sample amounts area 4 It filters and is equipped with whole blood filter membrane in area 3;When micro-fluidic chip is used for clinical diagnosis, whole blood is common test sample, and when detection is logical Often need to carry out whole blood separation with by whole blood serum or blood plasma separate, then reacted with reagent;It is arranged in chip Whole Blood Filtration area uses convenient for detection, while compared to whole blood is first quantified, then carrying out the mode of whole blood separation, injection port with It is equipped with Whole Blood Filtration area between sample amounts area, knot can be measured by the dosage of sample amounts area direct quantitative serum or blood plasma Fruit is more accurate.The material of whole blood filter membrane can be glass fibre, cotton linter fiber, polyester fiber, fiber or blend fibre;It is optional Ground, Whole Blood Filtration filter bed with a thickness of 0.2-2.5mm;The adsorption rate of Whole Blood Filtration filter bed is 4-150s/4cm, and water imbibition is 30-250mg/cm2
Referring to FIG. 5, optionally, liquid driving device is plunger pump 19.For structure, liquid driving device is settable It is a variety of, such as existing syringe pump, diaphragm pump, peristaltic pump, all can be realized drive liquid under pressure to core Presumptive area in piece should all fall into the protection scope of the utility model.Although syringe pump, diaphragm pump, peristaltic pump can drive Liquid flowing, but they cannot control liquid well and stop in specific position, and plunger pump can preferably solve this and ask Topic.The plunger pump that plunger pump suitable for the utility model can be well known to those skilled in the art, generally includes pump chamber 194 With plunger 193, pump chamber 194 is equipped with inlet 191 and liquid outlet 192, and the top of plunger 193 is inserted into pump chamber, plunger 193 Inner wall along pump chamber 194 is reciprocating in its axial direction;Valve V4, V6 are respectively equipped at inlet 191, liquid outlet 192. Since plunger pump is applied to imbibition, drain by more, two mouths being arranged on pump chamber are commonly known as " inlet and out liquid Mouthful ", but it should be recognized that " inlet and liquid outlet " herein is not limited to be used for feed liquor and out liquid, in the present embodiment, When plunger pump work, after the valve V4 at inlet 191 is opened, plunger is moved downward, and liquid closes on plunger pump inlet at this time The pressure of 191 one end becomes smaller, and causes liquid both ends to generate pressure difference, liquid is under the action of pressure difference to 191 side of inlet The valve V6 at liquid outlet is opened when liquid reaches pre-position to movement, so that chip interior and outside atmosphere connect Logical, in two sides air, (wherein the air of side enters chip interior through liquid outlet, inlet, the other side respectively for liquid two sides Air can enter chip interior from air inflow end mouth (such as injection port or separately the air subchannel that is arranged)) under the action of, pressure Power keeps balance, and liquid can rest on pre-position.
Liquid quantitative area (including the magnetic mark secondary antibody embedding area, enzyme mark primary antibody embedding area and sample amounts area sample of the present embodiment Product) can be realized " need to quantitatively liquid arrived behind the inlet influent quantification area in liquid quantitative area, hydraulically full quantification area Up to liquid outlet ", shape and structure can be selected as needed, and the utility model imposes any restrictions not to this, such as its It can be pipe shape, polygonal shape etc..
Optionally, liquid quantitative area is hexagonal structure.Specifically, the inlet and liquid outlet in liquid quantitative area are respectively Two of hexagonal structure are diagonal;Two diagonal angles are less than 120 °.
Optionally, the width of the inlet in liquid quantitative area is 0.3-3mm (preferably 0.8-1.5mm), is highly 0.3- 3mm;The width of the liquid outlet in liquid quantitative area is 0.3-3mm (preferably 0.8-1.5mm), is highly 0.3-3mm.Feed liquor mouth width Spend wide or narrow, excessive height or it is too low be unfavorable for quantitative progress, when inlet width is wide or excessive height, hold Easily cause liquid can not hydraulically full quantification area flow to its liquid outlet, cannot achieve accurate liquid quantitative in this way, and when into When liquid mouth width spends narrow or highly too low, then needs to increase accordingly requirement of the length to meet volume, may result in core in this way The increase of leaf length and the increase of chip volume.
Optionally, the surface in liquid quantitative area is the surface formed after hydrophilic surface is modified;Liquid quantitative area The width of inlet is 0.3-5mm, is highly 0.3-3mm;The width of the liquid outlet in liquid quantitative area is 0.3-5mm, is highly 0.3-3mm.Hydrophilic surface modification includes but is not limited to plasma, hydroxylating, carboxylated modification.The surface in liquid quantitative area into After row Hydrophilic modification, be more advantageous to the filling of liquid in the cavity, at this time can larger fluid quantification area appropriate inlet, The width of liquid outlet, so as to reduce the length in liquid quantitative area and chip.
Optionally, the surface in liquid quantitative area is the surface formed after hydrophobic surface is modified, liquid quantitative area The width of inlet is 0.3-2mm, is highly 0.3-3mm;The width of the liquid outlet in liquid quantitative area is 0.3-2mm, is highly 0.3-3mm.Hydrophobically modified includes but is not limited to hydrophobicity physical modification, (such as nanoparticle coating adds for hydrophobic chemical modification The alkyl etc. of long-chain).The surface in liquid quantitative area can prevent liquid wall built-up after hydrophobic surface is modified, and can guarantee liquid Body reaches liquid outlet after being full of in liquid quantitative area.
The present embodiment for Liquid identification device structure with no restriction, as long as being able to achieve the identification of liquid.Such as public affairs The number of opening is the Liquid identification that liquid sensing device disclosed in the patent application of " 105214744A " can be used as the utility model Device, but such liquid sensing device structure is complex, conductive pin need to be built into chip interior, and conductive pin and anti- It answers liquid to contact, will affect experimental result in any case.Preferably, Liquid identification device is set to the outside of matrix, passes through Optical Implementation detection, contactless mode, will not Interference Detection, also facilitate the processing and fabricating of matrix chip.
Preferably, Liquid identification device includes light source generation module 28 and photoelectric sensor 29;Liquid identification site includes Lower site for the upper site of positioned light source generation module 28 and for positioning photoelectric sensor 29, upper site and lower site point Not She Yu chip body outside, upper site, corresponding inlet or liquid outlet, the lower perpendicular line in site area are successively laid.Phase Ying Di, light source generation module 28, corresponding inlet or liquid outlet, the perpendicular line of photoelectric sensor 29 are successively laid.Due to liquid Body identification device can be set at the inlet or liquid outlet in liquid quantitative area or chemiluminescence detection area, therefore herein " corresponding Inlet or liquid outlet " correspond to the inlet or liquid outlet in liquid quantitative area or chemiluminescence detection area;For example, working as magnetic mark When Liquid identification device is arranged in the liquid outlet that secondary antibody embeds area, light source generation module, magnetic mark secondary antibody embed liquid outlet, the photoelectricity in area The perpendicular line of inductor is successively laid;When Liquid identification device is arranged in the inlet in magnetic mark secondary antibody embedding area, light source generates mould The perpendicular line of inlet, photoelectric sensor that block, magnetic mark secondary antibody embed area is successively laid;When the liquid outlet in sample amounts area is arranged When Liquid identification device, light source generation module, the liquid outlet in sample amounts area, the perpendicular line of photoelectric sensor are successively laid.
Using optical sensing come to Liquid identification, quantitative and control, relative to the way of contact of conducting type, the method is reduced Intervention of the metal to reaction system in chip, while such Liquid identification device can be set to outside micro-fluidic chip, be convenient for It is fixed in instrument, without being arranged on chip, reduces the difficulty of processing of chip.In use, only light source need to be generated mould Block and photoelectric sensor alignment liquid recognition site are placed.Specifically, chip body includes top plate 1 and bottom plate 20;Top plate 1 It is laminated and connects with bottom plate 20;The junction of top plate 1 and bottom plate 20 is provided with main fluid passageway and multiple functional areas;Light source generates mould The surface for being located in the corresponding position of top plate 1 corresponding with the inlet in liquid quantitative area or liquid outlet, photoelectricity is arranged in block 27 Inductor 28 is located in the underface of the corresponding position of bottom plate 20 corresponding with the inlet in liquid quantitative area or liquid outlet.
Light source generation module 28 is the module for being capable of providing light source, can be LED, halogen lamp, laser lamp etc..In light source Under irradiation, since gas, liquid are to the transmissivity and refractive index difference of light, the light intensity for being irradiated to photoelectric sensor is different, light Electric inductor can identify gas and liquid, to distinguish whether liquid arrives the point of induction.When liquid flow to liquid quantitative When entrance or liquid quantitative liquid outlet, Liquid identification device can be identified quickly, be determined to control liquid and stop flow into liquid Measure area.
Optionally, the connectivity part position of the other end of substrate luminescent solution subchannel 17 and the inlet in magnetic mark secondary antibody embedding area 7 In in the main fluid passageway of the inlet in magnetic mark secondary antibody embedding area 7;In one embodiment, " neighbouring " is interpreted as " distance herein 0.5~the 10mm of inlet (preferably 0.5~2mm) in magnetic mark secondary antibody embedding area 7 ".
Optionally, the cleaned liquid entrance 12 of cleaning solution, cleaning solution subchannel 18 enter magnetic mark secondary antibody embedding area 7 and are determined Amount;The connectivity part of the inlet in the other end and magnetic mark secondary antibody the embedding area 7 of cleaning solution subchannel 18 is located at neighbouring with inlet In main fluid passageway;In one embodiment, herein " neighbouring " be interpreted as " apart from magnetic mark secondary antibody embedding area 7 inlet 0.5~ 10mm (preferably 0.5~2mm) ".Preferably, the inlet of the other end of cleaning solution subchannel 18 and magnetic mark secondary antibody embedding area 7 Connectivity part substrate luminescent solution subchannel 17 the other end and magnetic mark secondary antibody embedding area 7 inlet connectivity part downstream, It can avoid substrate luminescent solution in this way and be cleaned liquid dilution.
Optionally, the other end of dilution subchannel 16 and enzyme mark primary antibody embedding area 5 inlet connectivity part be located at In the neighbouring main fluid passageway of the inlet in enzyme mark primary antibody embedding area 5;In one embodiment, herein " neighbouring " be interpreted as " away from 0.5~10mm of inlet (preferably 0.5~2mm) from enzyme mark primary antibody embedding area 5 ".
Optionally, the volume of injection port 2 is 5ul-300ul.
Optionally, the liquid outlet in Whole Blood Filtration area 3 is triangle liquid outlet;3 area of Whole Blood Filtration area is 30-300mm2, Width is 2-20mm, a length of 5-25mm, depth 0.3-3mm, and the angle of front end triangle is 15-160 DEG C.
Optionally, the volume in sample amounts area 4 is 1-50ul.
Optionally, the volume in enzyme mark primary antibody embedding area 5 is 5-50ul.
Optionally, the first mixing pipeline 6 and second mixes the width of pipeline 8 for 200-2000um, a length of 5mm-40mm, deeply For 0.2-3mm.
Optionally, the volume in magnetic mark secondary antibody embedding area 7 is 10-200ul.
Optionally, the volume in chemiluminescence detection area 9 is 10-200ul.
Next, describing a kind of inspection of the micro-fluidic chip of embodiment according to the present utility model in conjunction with Fig. 2~Fig. 6 Survey method.The method comprising the steps of 101 to step 110, and each step is specific as follows:
Step 101: will respectively with dilution storage pool 21, substrate luminescent solution storage pool 22, cleaning solution storage pool 23, plunger Closed pad 15 in pump 19, the steel needle of air communication insertion chip, wherein steel needle respectively with dilution entrance 10, substrate luminescent solution Entrance 11, filter washing water inlet 12, liquid driven power entrance 13, air intake 14 connect;Whole blood sample is added to injection port 2, It opens solenoid valve V4 and negative-pressure sucking is generated by plunger pump 19, whole blood sample is sucked into Whole Blood Filtration area 3.
After the gasket of steel needle insertion plunger pump 19, plunger pump 19 generates negative-pressure sucking, and whole blood sample is sucked whole blood Filtering area 3.
Step 102: whole blood sample completes filtered serum and is inhaled into sample amounts area 4, and by sample amounts area 4 into The photoelectric sensor (a1, a2) being arranged on liquid mouth and liquid outlet completes the quantitative measurment of serum.
When whole blood sample is by being that inductor output voltage value changes above photoelectric sensor a1, to system one Identification signal judges the flow locations of liquid in the chips.When sample passes through photoelectric sensor a2, judgement sample determines sample Amount area 4 is full of, and the intrinsic volume in the region is the quantitative values of sample.
Step 103: blocking injection port 2 and open solenoid valve V5, so that serum is inhaled into enzyme mark primary antibody embedding area 5.
Step 104: when the photoelectric sensor (b1) being arranged on the inlet in enzyme mark primary antibody embedding area 5 detects serum, Solenoid valve V5 is closed, solenoid valve V1 is opened, so that external sample dilution enters enzyme mark primary antibody embedding area 5 from solenoid valve V1.
Step 105: when the photoelectric sensor (b2) being arranged on enzyme mark primary antibody embedding 5 liquid outlet of area detects that external sample is dilute When releasing liquid, solenoid valve V1 is closed, solenoid valve V5 is opened, and positive pressure and negative-pressure sucking are sequentially generated by plunger pump 19, so that blood Clearly, external dilution liquid, the enzyme mark primary antibody embedded in advance are embedded in enzyme mark primary antibody and are flowed back and forth between area 5 and the first mixing pipeline 6 It redissolves, obtains the first mixed liquor.
Step 106: the first mixed liquor is inhaled into magnetic mark secondary antibody embedding area 7, and makes first by the second mixing pipeline 8 In conjunction with antigen-antibody, the reactant of formation is captured mixed liquor by magnetic bead, and magnetic bead is inhaled by the magnet in 7 outside of magnetic mark secondary antibody embedding area Attached and stable in magnetic mark secondary antibody embedding area 7, remaining reaction solution enters under the negative-pressure sucking of plunger pump 19 through liquid driven power Mouth discharge chip, then carries out next cleaning step.
Step 107: closing solenoid valve V5, and open solenoid valve V3, exterior washings liquid is made to enter magnetic mark secondary antibody embedding area 7, and the note that the photoelectric sensor (c1, c2) being arranged on 7 inlet of area and liquid outlet controls cleaning solution is embedded by magnetic mark secondary antibody Enter amount.
Step 108: after external cleaning solution and magnetic bead clean repeatedly, magnet 25a, 25b adsorb magnetic bead, are produced by plunger pump Liquid suction after cleaning is discharged in external waste liquid pool 24 by raw negative-pressure sucking.
Step 109: closing solenoid valve V3, open solenoid valve V2, external substrate luminescent solution is made to enter the embedding of magnetic mark secondary antibody Area 7, and pass through the injection rate of photoelectric sensor (c1, c2) control substrate luminescent solution.
Step 110: after substrate luminescent solution is sufficiently reacted with the antigen-antibody on magnetic bead, obtaining reaction solution, reaction solution quilt Chemiluminescence detection area 9 is transported, to complete chemiluminescence detection;Wherein, 9 inlet of chemiluminescence detection area and liquid outlet The photoelectric sensor (d1, d2) of upper setting is used to detect capacity and the position of reaction solution.
Reaction principle in the chemiluminescence micro-fluidic chip of the present embodiment between substance is the same as magnetic particle immunochemiluminescence Reaction principle, i.e. antigen in sample by and enzyme mark primary antibody (primary antibody is marked with the catalytic groups such as HRP, AP) combine, then with Magnetic mark secondary antibody (secondary antibody is fixed on magnetic bead), which combines, forms double antibodies sandwich compound, and magnet adsorbs magnetic bead, washes unbonded Antigen and enzyme mark primary antibody, substrate reactions liquid is added, the enzymes group catalysis substrate reaction solution such as HRP, AP marked on primary antibody shines. Luminous intensity and the amount of antigen are directly proportional.
Chemiluminescence microfluidic chip structure in the present embodiment is compact, such as magnetic mark secondary antibody embedding area is applied not only to embed Magnetic mark secondary antibody can also be used in quantifying substances luminescent solution as liquid quantitative area, and liquid quantitative area need not separately be arranged again, institute It states magnetic mark secondary antibody embedding Qu Haike and is further used as the chamber cleaned for magnetic bead, and magnetic bead need not be separately set again and clean chamber The volume of chip is greatly saved in room;Meanwhile reagent storage pool (such as quantifying substances luminescent solution storage pool, cleaning solution storage pool Deng) external to chip, reagent plates in chip compared with the existing technology, reduces the manufacture craft difficulty of chip, mentions The high accuracy of detection.
The chip body of chemiluminescence micro-fluidic chip in the present embodiment may include the top plate and bottom plate being stacked, and need On the settable top plate of the structure to be completed the process, bottom plate is only smooth plate, can further decrease the system of chip in this way Make technology difficulty, improves production efficiency.
Those of ordinary skill in the art will appreciate that realizing all or part of the process in above-described embodiment method, being can be with Relevant hardware is instructed to complete by computer program, the program can be stored in a computer-readable storage medium In, the program is when being executed, it may include such as the process of the embodiment of above-mentioned each method.Wherein, the storage medium can be magnetic Dish, CD, read-only memory (Read-Only Memory, ROM) or random access memory (Random Access Memory, RAM) etc..
The above is preferred embodiments of the present invention, it is noted that for the ordinary skill of the art For personnel, without departing from the principle of this utility model, several improvements and modifications can also be made, these are improved and profit Decorations are also considered as the protection scope of the utility model.

Claims (14)

1. a kind of liquid quantifying device, which is characterized in that the liquid quantitative area including matrix and in described matrix;
The liquid quantitative area has predetermined volume, and the both ends in the liquid quantitative area are respectively equipped with liquid quantitative entrance and liquid Body quantitatively exports, and liquid flows into the liquid quantitative area from liquid quantitative entrance, described in reaching behind the liquid quantitative area Liquid quantitative outlet;
The corresponding position of the liquid quantitative outlet is equipped with Liquid identification device, and the Liquid identification device reaches for identification The liquid of the liquid quantitative outlet.
2. liquid quantifying device according to claim 1, which is characterized in that the Liquid identification device is set to described matrix Outside.
3. liquid quantifying device according to claim 2, which is characterized in that the Liquid identification device includes that light source generates Module and photoelectric sensor;
The light source generation module, liquid quantitative outlet, the perpendicular line of the photoelectric sensor are successively laid.
4. liquid quantifying device according to claim 1, which is characterized in that the liquid quantitative inlet also is provided with liquid Identification device.
5. liquid quantifying device according to claim 4, which is characterized in that the Liquid identification device includes that light source generates Module and photoelectric sensor;The outside of described matrix is arranged in the Liquid identification device;
Liquid identification device set on the liquid quantitative exit is according to light source generation module, liquid quantitative outlet, light inductance The perpendicular line of device is answered successively to lay;
Liquid identification device set on the liquid quantitative inlet is according to light source generation module, liquid quantitative entrance, light inductance The perpendicular line of device is answered successively to lay.
6. liquid quantifying device according to claim 5, which is characterized in that described matrix includes top plate and bottom plate, described Top plate and bottom plate stacking connect;The junction of the top plate and the bottom plate is arranged in the liquid quantitative area;
It is arranged to go out with the liquid quantitative set on the light source generation module of the Liquid identification device in the liquid quantitative exit The surface of the corresponding position of the corresponding top plate of mouth, photoelectric sensor are arranged corresponding with liquid quantitative outlet The underface of the corresponding position of the bottom plate;
It is arranged to enter with the liquid quantitative set on the light source generation module of the Liquid identification device of the liquid quantitative inlet The surface of the corresponding position of the corresponding top plate of mouth, photoelectric sensor are arranged corresponding with the liquid quantitative entrance The underface of the corresponding position of the bottom plate.
7. liquid quantifying device according to claim 1, which is characterized in that the liquid quantitative area is hexagonal structure.
8. liquid quantifying device according to claim 1, which is characterized in that the liquid quantitative entrance in the liquid quantitative area Width be 0.3-3mm, be highly 0.3-3mm;The width of the liquid quantitative outlet in the liquid quantitative area is 0.3-3mm, high Degree is 0.3-3mm.
9. liquid quantifying device according to claim 1, which is characterized in that the surface for stating liquid quantitative area is through hydrophily The surface formed after surface modification;The width of the liquid quantitative entrance in the liquid quantitative area is 0.3-5mm, is highly 0.3- 3mm;The width of the liquid quantitative outlet in the liquid quantitative area is 0.3-5mm, is highly 0.3-3mm.
10. liquid quantifying device according to claim 1, which is characterized in that the surface in the liquid quantitative area is through dredging The width on the surface formed after aqueous surface modification, the liquid quantitative entrance in the liquid quantitative area is 0.3-2mm, is highly 0.3-3mm;The width of the liquid quantitative outlet in the liquid quantitative area is 0.3-2mm, is highly 0.3-3mm.
11. liquid quantifying device according to claim 1, which is characterized in that described matrix includes top plate and bottom plate, described Top plate and bottom plate stacking connect;The junction of the top plate and the bottom plate is arranged in the liquid quantitative area.
12. liquid quantifying device according to claim 11, which is characterized in that the top plate is equipped with groove, the bottom Plate is smooth plate, and the groove and the bottom plate cooperatively form the liquid quantitative area.
13. liquid quantifying device according to claim 1, which is characterized in that be additionally provided with fluid passage in described matrix, institute Fluid passage is stated to be connected to the liquid quantitative entrance.
14. liquid quantifying device according to claim 13, which is characterized in that be additionally provided with air subchannel in described matrix And air intake, one end of the air subchannel are connected to the fluid passage, the other end of the air subchannel and institute It states air intake to be connected to, liquid of the connectivity part of the air subchannel and the fluid passage adjacent to the liquid quantitative area is fixed Measure entrance.
CN201820619456.XU 2018-04-27 2018-04-27 A kind of liquid quantifying device Active CN209131768U (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108704677A (en) * 2018-04-27 2018-10-26 广州万孚生物技术股份有限公司 A kind of micro-fluidic chip and the analytical instrument containing it
CN108716938A (en) * 2018-04-27 2018-10-30 广州万孚生物技术股份有限公司 A kind of liquid quantifying device and its application
CN110426526A (en) * 2019-08-08 2019-11-08 重庆科技学院 A kind of multi-layer micro-fluidic chips for detection of heavy metal ion

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108704677A (en) * 2018-04-27 2018-10-26 广州万孚生物技术股份有限公司 A kind of micro-fluidic chip and the analytical instrument containing it
CN108716938A (en) * 2018-04-27 2018-10-30 广州万孚生物技术股份有限公司 A kind of liquid quantifying device and its application
CN108704677B (en) * 2018-04-27 2024-05-28 广州万孚生物技术股份有限公司 Microfluidic chip and analytical instrument comprising same
CN108716938B (en) * 2018-04-27 2024-06-07 广州万孚生物技术股份有限公司 Liquid quantifying device and application thereof
CN110426526A (en) * 2019-08-08 2019-11-08 重庆科技学院 A kind of multi-layer micro-fluidic chips for detection of heavy metal ion

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