CN209549516U - A kind of micro-fluidic chip and the analysis instrument containing it - Google Patents

A kind of micro-fluidic chip and the analysis instrument containing it Download PDF

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Publication number
CN209549516U
CN209549516U CN201820619055.4U CN201820619055U CN209549516U CN 209549516 U CN209549516 U CN 209549516U CN 201820619055 U CN201820619055 U CN 201820619055U CN 209549516 U CN209549516 U CN 209549516U
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liquid
chamber
micro
inlet
reagent
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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 micro-fluidic chip and containing its analysis instrument, which includes chip body and the injection port being arranged in the chip body, air intake, liquid driven power entrance, air subchannel, main fluid passageway and multiple function chambers;The main fluid passageway is connected to the multiple function chamber, and the liquid driven power entrance is for connecting the liquid driving device that liquid can be driven to flow in the main fluid passageway and multiple function chambers;The micro-fluidic chip of the utility model realizes that the identification of fluid sample positions and quantitatively, reduces the manufacture craft difficulty of chip, improve quantitative accuracy by specific liquid quantitative chamber, the quantitative and test especially suitable for whole blood sample.

Description

A kind of micro-fluidic chip and the analysis instrument containing it
Technical field
The utility model relates to medical instruments field more particularly to a kind of micro-fluidic chip and containing its analysis instrument.
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 of quantitative detection is less, and existing quantitative micro-fluidic chip preparation is complicated, raw Produce low efficiency.
Utility model content
To solve the above problems, one side the utility model provides a kind of micro-fluidic chip, sample may be implemented Accurate quantitative analysis, and structure is simple, reduces the manufacture craft difficulty of chip.
The technical solution adopted in the utility model are as follows: a kind of micro-fluidic chip comprising chip body and setting are in institute State injection port, air intake, liquid driven power entrance, air subchannel, main fluid passageway and the multiple functions in chip body Chamber;The main fluid passageway is connected to the multiple function chamber, and the liquid driven power entrance is for connecting liquid driven dress It sets to drive liquid to flow in the main fluid passageway and multiple function chambers;
At least one of the multiple function chamber is liquid quantitative chamber, and the liquid quantitative chamber has scheduled Volume, and Liquid identification site is provided at the liquid outlet of liquid quantitative chamber, need to liquid quantitatively from the liquid quantitative The inlet of chamber flows into the liquid quantitative chamber, full of reaching the liquid outlet after the liquid quantitative chamber;
The liquid quantitative chamber includes sample amounts chamber, and fluid sample flows into the sample amounts through the injection port Chamber is quantified;One end of the air subchannel is connected to the air intake, the other end and the sample amounts chamber Main fluid passageway connection between the injection port, the other end of the air subchannel and the connection of the main fluid passageway Locate the neighbouring sample amounts chamber.
The liquid driving device is plunger pump in one of the embodiments,.
Liquid identification site is provided at the inlet of liquid quantitative chamber in one of the embodiments,.
The liquid quantitative chamber further includes reagent quantitative chamber in one of the embodiments, the reagent quantitative chamber The inlet of room is connected to one end of reagent subchannel, and the other end of the reagent subchannel is connected to reagent inlet, the examination Agent quantifies the downstream that chamber is set to the sample amounts chamber.
The function chamber includes detection chambers in one of the embodiments, and the detection chambers have scheduled appearance Product, and Liquid identification site is provided at the liquid outlet of the detection chambers, liquid to be detected is through the detection chambers Inlet flows into the detection chambers, full of reaching liquid outlet after the detection chambers.
Liquid identification site is also equipped at the inlet of the detection chambers in one of the embodiments,.
The Liquid identification site is for positioning Liquid identification device in one of the embodiments,;The Liquid identification Device includes light source generation module and photoelectric sensor;
The Liquid identification site includes upper site for positioning the light source generation module and for positioning the light The lower site of electric inductor, the upper site and the lower site are respectively arranged on the outside of the top plate and the bottom plate, described The position in upper site and lower site and corresponding liquid outlet or inlet are corresponding, so that the light source after positioning generates Module, corresponding liquid outlet or inlet, the perpendicular line of the photoelectric sensor are successively laid.
The liquid quantitative chamber is the chamber of hexagonal structure in one of the embodiments,.
The width of the inlet of the liquid quantitative chamber is 0.3-3mm in one of the embodiments, is highly 0.3- 3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3-3mm, is highly 0.3-3mm;Or
The surface of the liquid quantitative chamber is the surface formed after hydrophilic surface is modified;The liquid quantitative chamber The width of the inlet of room is 0.3-5mm, is highly 0.3-3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3- 5mm is highly 0.3-3mm;Or
The surface of the liquid quantitative chamber is the surface formed after hydrophobic surface is modified, the liquid quantitative chamber The width of the inlet of room is 0.3-2mm, is highly 0.3-3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3- 2mm is highly 0.3-3mm.The chip body includes top plate and bottom plate in one of the embodiments,;The top plate and institute State bottom plate stacking connection;The junction of the top plate and the bottom plate is provided with the main fluid passageway and the multiple functional chamber Room.
The bottom plate is smooth plate in one of the embodiments, be provided on the top plate micropore, microchannel or Microcavity body is to form the injection port, liquid driven power entrance, main fluid passageway or function chamber with the bottom plate.
Whole Blood Filtration chamber is equipped between the injection port and the sample amounts chamber in one of the embodiments, Whole blood filter membrane is equipped in the Whole Blood Filtration chamber.
On the other hand, the utility model additionally provides a kind of analysis instrument with micro-fluidic chip comprising instrument frame Frame, liquid driving device, detection device and above-described micro-fluidic chip;Wherein, the micro-fluidic chip is mounted on described In apparatus frame;The liquid driving device is connected with the liquid driven power entrance of the micro-fluidic chip;The detection device For receiving the detection signal for handling the micro-fluidic chip and issuing.
The liquid quantitative chamber of the micro-fluidic chip further includes reagent quantitative chamber, institute in one of the embodiments, The inlet for stating reagent quantitative chamber is connected to one end of reagent subchannel, the other end and reagent inlet of the reagent subchannel Connection, the reagent quantitative chamber are set to the downstream of the sample amounts chamber;
The analysis instrument further includes reagent storage pool, and the reagent storage pool and the reagent inlet can connect to on-off It is logical.
The liquid driving device is plunger pump in one of the embodiments,.
Compared with the existing technology, the utility model has the following beneficial effects:
The micro-fluidic chip of the utility model can be convenient for quantifying for fluid sample due to being provided with sample amounts chamber, and Without separately quantitative outside chip, so that chip is using more convenient, while the clever structure combination liquid of liquid quantitative chamber Recognition site, it can be achieved that fluid sample accurate quantitative analysis, while Liquid identification device can be not fixed on chip (it can be set to chip Outside), be capable of the structure of facilitating chip in this way, reduce its producting process difficulty, substantially increase production efficiency, it is particularly suitable In the quantitative and test of whole blood sample.
The chip body of the micro-fluidic chip of the utility model may include the top plate and bottom plate being stacked, and need to process At the settable top plate of structure on, bottom plate is only smooth plate, and the manufacture craft that can further decrease chip in this way is difficult Degree improves production efficiency.
Detailed description of the invention
Fig. 1 is a kind of structural schematic diagram of embodiment of micro-fluidic chip 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 arrangement structure for sensor figure of embodiment of micro-fluidic chip provided by the utility model;
Fig. 4 is the schematic cross-section of magnet setting position when micro-fluidic chip provided by the utility model uses;
Fig. 5 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, empty Gas 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
A kind of micro-fluidic chip is present embodiments provided, which includes chip body and be arranged described Injection port, air intake, liquid driven power entrance, air subchannel, main fluid passageway and multiple functional chambers in chip body Room;It is specifically described below.
In the present embodiment, main fluid passageway is connected to multiple function chambers, to guide stream of the fluid between function chamber It is dynamic.Liquid driven power entrance is for connecting liquid driving device to drive liquid in the main fluid passageway and multiple function chambers Middle flowing.
In the present embodiment, function chamber at least has the function of receiving, it is preferable that function chamber accommodates function except tool Outside, also there is other function, other function can be realization in functional chamber room, be also possible to function chamber in conjunction with its outside Necessary parts (these necessary components can fix in chip exterior, no setting is required in the chip or its surface) realize jointly.
In the present embodiment, at least one liquid quantitative chamber in multiple function chambers;Liquid quantitative chamber has pre- Fixed volume, and be provided with Liquid identification site at the inlet and liquid outlet of liquid quantitative chamber, need to liquid quantitatively from The inlet of the liquid quantitative chamber flows into the liquid quantitative chamber, described out full of arrival after the liquid quantitative chamber Liquid mouth.Liquid identification site is for positioning or fixing liquid identification device, Liquid identification device liquid for identification, when liquid arrives When at up to liquid outlet, Liquid identification device can provide signal, and liquid quantitative chamber is full of by indicating liquid, control liquid at this time Driving device stops driving liquid, realizes liquid quantifying in liquid quantitative chamber.
The quantity of liquid quantitative chamber, (such as fluid sample, reaction reagent, the sample treatment examination of its quantitative kind of liquid Agent etc.), setting position and the type of other function chamber can be selected according to actual needs.
In the present embodiment, liquid quantitative chamber includes sample amounts chamber, and fluid sample flows into sample through the injection port Product quantify chamber and are quantified;One end of air subchannel is connected to air intake, the other end and sample amounts chamber and sample introduction Main fluid passageway connection between mouthful, the other end of air subchannel and the connectivity part of main fluid passageway are adjacent to sample amounts chamber Room.
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 is under the action of liquid driving device through injection port from sample amounts chamber Inlet flows into sample amounts chamber, when at the liquid outlet that fluid sample flow to sample amounts chamber, i.e., fixed full of sample Chamber is measured, the Liquid identification device positioned on the Liquid identification site of liquid outlet is now placed in and issues indication signal, control air Entrance is opened, and 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 more Greatly, therefore fluid sample rests on air subchannel and the connectivity part of main fluid passageway does not continue to flow into sample amounts chamber, Fluid sample quantifying in sample amounts chamber can be completed.Fluid sample after quantitative can be in the effect of liquid driving device Under continue to flow in other function chambers, complete subsequent reaction.
The micro-fluidic chip of the present embodiment can be quantified due to being provided with sample amounts chambers convenient for fluid sample, and nothing Need to be separately quantitative outside chip, so that chip is using more convenient, while clever structure the combination liquid knowledge of liquid quantitative chamber Other site, it can be achieved that fluid sample accurate quantitative analysis, while may be selected to be not fixed Liquid identification device that (it can be set to core on chip The outside of piece), it is capable of the structure of facilitating chip in this way, reduces its producting process difficulty, substantially increases production efficiency, it is especially suitable For the processing of whole blood sample and quantitative.
Above-mentioned " liquid quantitative chamber includes sample amounts chamber ", which is interpreted as liquid quantitative chamber, should at least have use In this seed type of the sample amounts chamber of quantitative liquid sample, naturally it is also possible to further comprise for other quantitative kind of liquid Liquid quantitative chamber, such as be used for quantitative reagent reagent quantitative chamber.
Optionally, it is equipped with Whole Blood Filtration chamber between injection port and sample amounts chamber, is equipped in Whole Blood Filtration chamber complete Blood filter membrane;When micro-fluidic chip is used for clinical diagnosis, whole blood is common test sample, and when detection usually requires to carry out whole blood Separation with by whole blood serum or blood plasma separate, then reacted with reagent;Whole Blood Filtration chamber is set in chip, just It is used in detection, while compared to whole blood is first quantified, then the mode of whole blood separation is carried out, in injection port and the sample amounts chamber Whole Blood Filtration chamber is equipped between room, can be by the dosage of sample amounts chamber direct quantitative serum or blood plasma, measurement result is more It is accurate.The material of the whole blood filter membrane can be glass fibre, cotton linter fiber, polyester fiber, fiber or blend fibre;It is optional Ground, the Whole Blood Filtration filter bed with a thickness of 0.2-2.5mm;The adsorption rate of the Whole Blood Filtration filter bed is 4-150 s/4cm, Water imbibition is 30-250mg/cm2
Optionally, the volume of the injection port is 10ul-300ul.
Optionally, the liquid outlet in the Whole Blood Filtration area is triangle liquid outlet;Whole Blood Filtration area area is 30- 300mm2, width 2-20mm, a length of 5-25mm, depth 0.3-3mm, the angle of front end triangle is 15-160 DEG C.
Preferably, liquid quantitative chamber includes reagent quantitative chamber, the inlet of reagent quantitative chamber and reagent subchannel One end connection, the other end of reagent subchannel is connected to reagent inlet, and reagent quantitative chamber is under sample amounts chamber Trip, reagent enter reagent quantitative chamber through reagent inlet, reagent subchannel and are quantified.It is quantified using micro-fluidic chip When detection, fluid sample (testing liquid flowed into from injection port) and reagent (such as reaction reagent, sample processing reagent etc.) Amount quantified, the quantitative needs of usual reagent in the chip portion complete, fluid sample is selectively in micro-fluidic core Realize that quantitatively reagent quantitative chamber is used for quantifying for reagent in the present embodiment outside piece.
The quantity of reagent quantitative chamber can for one, it is two or more, can be carried out according to the actual needs of micro-fluidic chip Selection.Such as when micro-fluidic chip is chemiluminescence micro-fluidic chip, in order to realize chemiluminescence quantitative detection, reagent quantitative Chamber should be arranged one at least with for quantifying substances luminescent solution, remaining reacts necessary substance such as enzyme mark primary antibody, magnetic mark two It is anti-to be embedded in respectively in enzyme mark primary antibody embedding chamber and magnetic mark secondary antibody embedding the two functional chamber rooms of chamber;Preferably, magnetic mark It is reagent quantitative chamber that secondary antibody, which embeds chamber, is inside not only embedded with magnetic mark secondary antibody, it may also be used for quantifying substances luminescent solution;It is more excellent Selection of land, magnetic mark secondary antibody embedding chamber are also used to magnetic bead cleaning.
Optionally, reagent inlet can be connect to on-off with reagent storage pool by valve, and reagent storage pool is equipped with and the external world The opening of air communication, reagent storage pool, which is equipped with opening, to be convenient for liquid driving device will be in the liquid drain to chip in it; For the ease of the preparation of chip, it is preferable that reagent storage pool is set to the outside of micro-fluidic chip, and when use pacifies reagent storage pool At reagent inlet, to introduce the reagents into chip.
Optionally, Liquid identification site is also equipped at the inlet of liquid quantitative chamber.This Liquid identification site is same It can be used for positioning or fixing liquid identification device, setting can be convenient for being monitored the flowing of liquid in chip, controlling.
Portion in the chip needs two kinds of liquid contacts to the mixing of two kinds of liquid of realization, and gap is not present in centre, and The micro-fluidic chip of the utility model to realize the contact of quantitative and two kinds of liquid of liquid simultaneously, and this requires wherein one Liquid after kind is quantitative rests on pre-position, and another liquid preferably begins to flow into liquid quantitative chamber from this predetermined position Room is realized quantitatively, and at the optimal selection in this predetermined position, that is, liquid quantitative chamber inlet in liquid quantitative chamber;In Liquid identification site is set to position or fix liquid identification device, this Liquid identification device can provide wherein one at inlet The feed liquor signal of the stop indication signal of kind liquid and another liquid, the Liquid identification at the liquid outlet of liquid quantitative chamber Under the cooperation of device, quantitative and two kinds of liquid the contact of liquid can be realized.Next, with the mixed of fluid sample and reagent Example is combined into illustrate the application method of lower micro-fluidic chip:
Micro-fluidic chip is in use, reagent inlet and reagent storage pool can be connect to on-off by valve, reagent storage pool Equipped with the opening being connected to outside air.Fluid sample after sample amounts chamber is quantitative is under the action of liquid driving device When flowing at the inlet of reagent quantitative chamber, the Liquid identification device that is positioned on the Liquid identification site of reagent quantitative chamber Signal is obtained, control liquid driving device stops driving effect, and fluid sample stops flowing at this time, and the front end of fluid sample stops At inlet;Then, air intake is closed, the valve between reagent inlet and reagent storage pool is opened, reagent drives in liquid Enter in reagent quantitative chamber under the action of dynamic device from reagent inlet through the inlet of reagent subchannel, reagent quantitative chamber, When flowing to the liquid outlet of reagent quantitative chamber, reagent is full of reagent quantitative chamber, closes reagent inlet at this time and reagent stores Valve between pond opens air intake, the quantitative reagent of reagent quantitative chamber and fluid sample in the work of liquid driving device Continue to flow under, and can realize positive reverse movement under the positive pressure of liquid driving device, negative pressure alternating action and realize mixed It closes and/or reacts.
In order to reduce influence of the reagent subchannel for the Liquid identification device at reagent quantitative chamber inlet, it is convenient for liquid Body flows into reagent quantitative chamber from from inlet, and specifically, one end of the reagent subchannel passes through the main fluid passageway It is connected to the inlet of reagent quantitative chamber, the connectivity part of the reagent subchannel and the main fluid passageway is adjacent to reagent quantitative At the inlet of chamber, so that it is quantitative in controlled range, reduce quantitative error, for example, the reagent subchannel and the master The distance of inlet of the connectivity part of fluid channel apart from reagent quantitative chamber is 0.5-10mm (preferably 0.5-2mm).
Embodiment 2
Please refer to FIG. 1 to FIG. 5, present embodiments provide a kind of chemiluminescence micro-fluidic chip comprising chip body, with And injection port 2, liquid driven power entrance 13, substrate luminescent solution entrance 11, filter washing water inlet 12, bottom in chip body are set Object luminescent solution subchannel 17, cleaning solution subchannel 18, main fluid passageway and multiple function chambers;It is specifically described below.
In the present embodiment, main fluid passageway is connected to multiple function chambers, to guide stream of the fluid between function chamber It is dynamic.
Function chamber includes the sample amounts area 4 being sequentially communicated by main fluid passageway, the embedding of enzyme mark primary antibody area 5, magnetic mark Secondary antibody embeds area 7 and 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;Sample Quantitative chamber 4 and magnetic mark secondary antibody embedding area 7 are liquid quantitative chamber;Fluid sample flows into sample amounts chamber 4 through injection port It is quantified;Liquid quantitative chamber is used for quantitative liquid, enters liquid quantitative chamber to quantitative liquid (such as substrate luminescent solution) Behind room, quantitative (obtaining desired amount of liquid) can be realized in liquid quantitative chamber, with quantitative fluid sample or its He reacts at reaction reagent, to realize quantitative detection.
In the present embodiment, liquid quantitative chamber has scheduled volume, and sets at the liquid outlet of liquid quantitative chamber It is equipped with Liquid identification site, the liquid that need to be quantified quantifies chamber from the inlet influent of liquid quantitative chamber, hydraulically full Liquid outlet is reached after quantitative chamber;For positioning or fixing liquid identification device, Liquid identification device is used in Liquid identification site Identify liquid.When liquid reaches at liquid outlet, Liquid identification device can provide liquid arriving signal, and indicating liquid is by liquid Quantitative chamber is full of, and is controlled liquid driving device at this time and is stopped driving liquid, liquid can be realized in liquid quantitative chamber It is quantitative.Chemiluminescence micro-fluidic chip realizes determining for liquid by specific liquid quantitative chamber combination liquid driving device Amount, can be improved quantitative accuracy.By being provided with sample amounts chambers, can be quantified convenient for fluid sample, without It is separately quantitative outside chip so that chip use it is more convenient.
In the present embodiment, the air subchannel 27 that air intake 14 is additionally provided on micro-fluidic chip and is communicated therewith, it is empty One end of gas subchannel 27 is connected to air intake 14, and the main fluid between the other end and sample amounts chamber 4 and injection port 2 is logical Road connection, the other end of air subchannel 27 and the connectivity part of main fluid passageway are adjacent to sample amounts chamber 4;In one embodiment In, " neighbouring " herein is interpreted as " 0.5~10mm of inlet (preferably 0.5~2mm) apart from sample amounts chamber 4 ".
Chemiluminescence detection area 9 is for accommodating chemiluminescence reaction product, to complete detection in conjunction with external detection device Process.
In the present embodiment, injection port 2 is connected to main fluid passageway respectively with liquid driven power entrance 13, driving force entrance 13 are used to connect liquid driving device to drive liquid inflow or downstream chamber;Injection port 2 is for introducing fluid sample In main fluid passageway, fluid sample enters each function chamber 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, air intake and the air pipeline of chip exterior can be led to by valve It connects disconnectedly, enters chip interior to control air;Substrate luminescent solution entrance 11, filter washing water inlet 12 shine with substrate respectively 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 solution The opening being connected to outside air is respectively equipped on storage pool 23;Liquid driving device is mounted at liquid driven power entrance 13, It is flowed to liquid in driving chip;The outside in magnetic mark secondary antibody embedding area 7 is fixed with magnet (such as magnet 25a, 25b), so as to Fixed magnetic bead 26.It is liquid quantitative chamber 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) it is fixed from the inlet of sample amounts chamber inflow sample through injection port under the action of liquid driving device It measures in chamber, when at the liquid outlet that fluid sample flow to sample amounts chamber, that is, is full of sample amounts chamber, is now placed in out The Liquid identification device positioned on the Liquid identification site of liquid mouth issues indication signal, and control air intake is opened, due to air Driving pressure needed for the flowing of air is small in subchannel, and the pressure driven needed for the flowing of fluid sample is bigger, therefore liquid Sample rests on air subchannel and the connectivity part of main fluid passageway does not continue to flow into sample amounts chamber, and liquid can be completed Sample quantifying in sample amounts chamber.Fluid sample after quantitative continues to flow to enzyme mark under the action of liquid driving device Primary antibody embeds area 5, and the enzyme mark primary antibody hybrid reaction wherein embedded, reaction solution reaches magnetic mark secondary antibody and embeds area 7 thereafter, and wherein The magnetic mark secondary antibody of embedding continuess to mix reaction, and the reactant of double antibodies sandwich structure is formed on magnetic bead, and magnetic bead is adsorbed by magnet, instead Object is answered to stablize in magnetic mark secondary antibody embedding area 7 under the action of magnetic bead, and remaining reaction solution is in the effect of liquid driving device It is lower that chip is discharged through liquid driven power entrance 13;Then, the air inflow end mouth (such as sample inlet) on chip is closed, is opened clear Valve V3 between washing lotion storage pool 23 and filter washing water inlet 12, cleaning solution cleaned liquid branch under the action of liquid driving device Channel 18 enters magnetic mark secondary antibody embedding area 7 to clean to magnetic bead therein, when magnetic mark secondary antibody embedding area 7 is completed to cleaning solution It is quantitative when, can close the valve V3 between cleaning solution storage pool 23 and filter washing water inlet 12, open air inflow end mouth, clearly Chip is discharged through liquid driven power entrance 13 under the action of liquid driving device in liquid after washing, in order to guarantee cleaning effect, It can clean for several times that (magnetic bead cleaning way is not limited to mode described herein, can also be for example, by moving in cleaning solution repeatedly The mode of magnet realizes the cleaning of magnetic bead);The air inflow end mouth (such as sample inlet) being then switched off on chip opens substrate hair Valve V2 between light liquid storage pool 22 and substrate luminescent solution entrance 11, substrate luminescent solution pass through under the action of liquid driving device Substrate luminescent solution subchannel 19 enters magnetic mark secondary antibody and embeds area 7, when magnetic mark secondary antibody embedding area 7 completes to quantify substrate luminescent solution When, 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 are no longer flow into magnetic mark secondary antibody embedding area 7, open the air inflow end mouth (such as sample inlet) on chip, The reactant of substrate luminescent solution and magnetic capture after quantitative carries out luminescence-producing reaction, removes magnet later, and magnetic mark secondary antibody embeds area 7 In reaction solution flow into chemiluminescence detection area 9 under the action of liquid driving device and 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 chamber, and liquid quantitative chamber 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, greatlys save The volume of chip;Meanwhile reagent storage pool (such as substrate luminescent solution storage pool, cleaning solution storage pool) is external to chip, Reagent plates in chip compared with the existing technology, reduces the manufacture craft difficulty of chip, improves the accuracy of detection.
It should be noted that main fluid passageway and multiple function chambers can pass through laser processing, model injection molding etc. Various ways shape inside chip body, can also by being set as the top plate and bottom plate of separate type, on top plate or bottom plate plus Work goes out specific shape, is then 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 function chambers;It is highly preferred that bottom plate 20 is smooth plate, micropore, microchannel is arranged in top plate 20 Or microcavity body is to cooperatively form injection port 2, liquid driven power entrance 13, substrate luminescent solution entrance 11, filter washing water inlet with bottom plate 12, substrate luminescent solution subchannel 17, cleaning solution subchannel 18, main fluid passageway or multiple function chambers, such micro-fluidic core Piece preparation get up it is more convenient, further reduced producting process difficulty, only required specific structure need to be processed on top plate i.e. Can, further improve production efficiency.In one embodiment, bottom plate 20 is smooth plate, and top plate 1 is equipped with multiple micro- logical To be combined to form main fluid passageway with bottom plate 20, top plate 1 is equipped with multiple microcavitys to be combined to form multiple functions with bottom plate 20 in road Chamber, top plate 1 form injection port 2, liquid driven power entrance 13, substrate luminescent solution equipped with the combination of multiple Kong Yiyu bottom plates 20 and enter Mouth 11 and 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 site is also equipped at the inlet of liquid quantitative chamber.This Liquid identification site is set Two kinds of quantitative liquid can be can also be achieved convenient for being monitored, controlling to the flowing of liquid in chip and bubble that may be present by setting Mixing between mixing between body, such as fluid sample and reagent (such as reaction reagent, sample processing reagent).Further Ground, it is also liquid quantitative chamber that enzyme mark primary antibody, which embeds area 5, is additionally provided with dilution entrance 10 and dilution subchannel in chip body 16;One end of dilution subchannel 16 is connected to dilution entrance 10, and the inlet in the other end and enzyme mark primary antibody embedding area 5 connects Logical, sample diluting liquid enters enzyme mark primary antibody embedding area 5 through dilution entrance, dilution subchannel and is quantified.Further, Be respectively arranged with Liquid identification site at the inlet and liquid outlet in enzyme mark primary antibody embedding area 5, need to liquid quantitatively from its feed liquor Mouth flows into enzyme mark primary antibody and embeds area 5, reaches liquid outlet after embedding area 5 full of enzyme mark primary antibody.Sample diluting liquid can not only dilute Fluid sample (such as serum, blood plasma), reduces its concentration and viscosity, wherein the substance contained can also reduce the sheet of fluid sample Floors, so that detection is more accurate, while sample diluting liquid can preferably redissolve enzyme mark primary antibody;In this technical solution, enzyme Mark primary antibody embedding area can be used for quantifying sample diluting liquid, quantitative without realizing quantifying for sample diluting liquid in chip exterior Sample diluting liquid can embed area in enzyme mark primary antibody and be mixed with quantitative fluid sample, can save manpower, it is more convenient to operate. In use, dilution entrance 10 can be connect to on-off with dilution storage pool 21 by valve V1, on dilution storage pool 21 Equipped with the opening being connected to outside air;The fluid sample (serum or blood plasma such as after diluted) of predetermined amount is in liquid It is flow at the inlet in enzyme mark primary antibody embedding area 5 from injection port 2 through main fluid passageway under the action of driving device, closes chip On air intake (such as sample inlet), open the valve V1 between dilution storage pool 21 and dilution entrance 10, sample is dilute It releases liquid and enters enzyme mark primary antibody embedding area 5 through dilution subchannel 16 under the action of liquid driving device, when it is full of enzyme mark one Anti- embedding area 5, when reaching at the liquid outlet in enzyme mark primary antibody embedding area 5, close dilution storage pool 21 and dilution entrance 10 it Between valve V1, open air inflow end mouth (such as sample inlet), fluid sample and sample diluting liquid can be filled in liquid driven Continue to flow under the suction function set, and can be in the positive pressure of liquid driving device, negative pressure alternating action in main fluid passageway, enzyme mark Primary antibody, which embeds, realizes 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 in the inlet in chemiluminescence detection area 9 and goes out Liquid identification site is respectively arranged at liquid mouth, liquid to be detected flows into chemistry hair through the inlet in chemiluminescence detection area 9 Light detection area 9, full of liquid outlet is reached behind chemiluminescence detection area 9, the volume in chemiluminescence detection area 9 is less than or equal to magnetic mark two The volume in anti-embedding area 7.The Liquid identification site being arranged at the liquid outlet in chemiluminescence detection area 9 can be used for positioning or fixer Body identification device, reaction solution after substrate luminescent solution is reacted with the reactant of magnetic capture reach chemiluminescence detection area Liquid outlet at when, Liquid identification device issue signal, liquid driving device control reaction solution stop flowing, can carry out at this time Detection.
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, liquid driving device is plunger pump 19, and the description as described in plunger pump is suitable for this implementation in embodiment 3 Example.
Optionally, fluid sample is whole blood, and Whole Blood Filtration area 3, whole blood are equipped between injection port 7 and sample amounts chamber 4 Whole blood filter membrane is equipped in filtering area 3;When micro-fluidic chip is used for clinical diagnosis, whole blood is common test sample, when detection It is generally necessary to carry out whole blood separation with by whole blood serum or blood plasma separate, then reacted with reagent;It is set in chip Whole Blood Filtration area is set, is used convenient for detection, while compared to whole blood is first quantified, then the mode of whole blood separation is carried out, in injection port Between sample amounts chamber be equipped with Whole Blood Filtration area, can by the dosage of sample amounts chamber direct quantitative serum or blood plasma, Measurement result is more accurate.The material of whole blood filter membrane can be glass fibre, cotton linter fiber, polyester fiber, fiber or blended fibre Dimension;Optionally, Whole Blood Filtration filter bed with a thickness of 0.2-2.5mm;The adsorption rate of Whole Blood Filtration filter bed is 4-150 s/4cm, Water imbibition is 30-250mg/cm2
The description as described in liquid quantitative chamber is suitable for above-described liquid quantitative chamber (including magnetic mark in embodiment 4 Secondary antibody embeds area 7, enzyme mark primary antibody embedding area 5 and sample amounts chamber 4), details are not described herein.
Description is suitable for above-described Liquid identification as described in Liquid identification site and Liquid identification device in embodiment 5 Site and Liquid identification device, details are not described herein.
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 to quantitative chamber.
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 of sample amounts chamber 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. 1 to FIG. 5 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.
Step 102: whole blood sample completes filtered serum and is inhaled into sample amounts chamber 4, and by sample amounts chamber The photoelectric sensor (a1, a2) being arranged on 4 inlet of room 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 chamber 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.
Embodiment 3
Referring to FIG. 5, the utility model provides the liquid driving device of function described in achievable embodiment 1 or 2.In In the present embodiment, liquid driving device is plunger pump 19.
For structure, liquid driving device may be configured as a variety of, such as existing syringe pump, diaphragm pump, peristaltic pump, all It is that by and liquid is driven to the presumptive area to chip under pressure, the protection model of the utility model should all be fallen into It encloses.Although syringe pump, diaphragm pump, peristaltic pump can drive liquid to flow, they cannot control liquid in certain bits well Stop is set, and plunger pump can preferably solve this problem.Plunger pump suitable for the utility model can be art technology Plunger pump known to personnel, generally includes pump chamber and plunger, and pump chamber is equipped with inlet 191 and liquid outlet 192, plunger In 193 top insertion pump chamber, plunger 193 is reciprocating in its axial direction along the inner wall of pump chamber 194;Inlet 191 goes out Valve V4, V6 are respectively equipped at liquid mouth 192.Since plunger pump is applied to imbibition, drain, two be arranged on pump chamber by more Mouth is commonly known as " inlet and liquid outlet ", but it should be recognized that " inlet and liquid outlet " herein is not limited to use In feed liquor and liquid out, in the present embodiment, when plunger pump work, after the valve V4 at inlet 191 is opened, plunger is transported downwards Dynamic, the pressure that liquid closes on one end of plunger pump inlet 191 at this time becomes smaller, and liquid both ends is caused to generate pressure difference, and liquid exists It is moved under the action of pressure difference to 191 direction of inlet, when liquid reaches pre-position, opens the valve at liquid outlet V6 so that chip interior is connected to outside atmosphere, liquid two sides respectively two sides air (wherein the air of side through liquid outlet, Inlet enters chip interior, the air of the other side can from air inflow end mouth (such as injection port or separately the air that is arranged to logical Road) enter chip interior) under the action of, pressure keeps balance, and liquid can rest on pre-position.
Embodiment 4
Fig. 1 and Fig. 3 are please referred to, the utility model provides the liquid quantitative chamber of function described in achievable embodiment 1 or 2 Room.
It should be noted that the liquid quantitative chamber of the utility model can be realized " need to liquid quantitatively from liquid quantitative The inlet influent of chamber quantifies chamber, reaches liquid outlet after hydraulically full quantitative chamber ", shape and structure can root According to being selected, the utility model imposes any restrictions not to this, such as it can be pipe shape, polygonal shape etc..
Realize that " liquid that need to be quantified flows into the liquid quantitative chamber from the inlet of the liquid quantitative chamber, is full of Reach the liquid outlet after the liquid quantitative chamber " mode there are many, such as control liquid quantitative chamber width and height Degree carries out hydrophilic and hydrophobic processing etc. on the surface of liquid quantitative chamber.
In the present embodiment, the liquid quantitative chamber is the chamber of hexagonal structure.Optionally, the liquid quantitative chamber The inlet and liquid outlet of room are respectively that two of the hexagonal structure are diagonal;Described two diagonal angles are less than 120 °.
Optionally, the width of the inlet of liquid quantitative chamber is 0.3-3mm (preferably 0.8-1.5mm), is highly 0.3-3mm;The width of the liquid outlet of liquid quantitative chamber is 0.3-3mm (preferably 0.8-1.5mm), is highly 0.3-3mm.Into Liquid mouth width spend wide or narrow, excessive height or it is too low be unfavorable for quantitative progress, when inlet width is wide or high spends Gao Shi be easy to cause liquid hydraulically full can not quantify chamber and flow to its liquid outlet, it is fixed to cannot achieve accurate liquid in this way Amount, and when inlet width is narrow or height is too low, then it needs to increase accordingly requirement of the length to meet volume, in this way may It will lead to the increase of chip length and the increase of chip volume.
Optionally, the surface of liquid quantitative chamber is the surface formed after hydrophilic surface is modified;Liquid quantitative chamber The width of the inlet of room is 0.3-5mm, is highly 0.3-3mm;The width of the liquid outlet of liquid quantitative chamber is 0.3-5mm, Height is 0.3-3mm.Hydrophilic surface modification includes but is not limited to plasma plus hydroxyl, carboxyl modified.Liquid quantitative chamber Surface carry out Hydrophilic modification after, be more advantageous to the filling of liquid in the cavity, at this time can larger fluid appropriate quantify chamber Inlet, liquid outlet width, so as to reduce the length of liquid quantitative chamber and chip.
Optionally, the surface of liquid quantitative chamber is the surface formed after hydrophobic surface is modified, liquid quantitative chamber The width of the inlet of room is 0.3-2mm, is highly 0.3-3mm;The width of the liquid outlet of liquid quantitative chamber is 0.3-2mm, Height is 0.3-3mm.Hydrophobically modified includes but is not limited to hydrophobicity physical modification, hydrophobic chemical modification (such as nanoparticle Coating, the alkyl for lengthening chain etc.).The surface of liquid quantitative chamber can prevent liquid wall built-up after hydrophobic surface is modified, and It can guarantee and reach liquid outlet after liquid is full of in liquid quantitative chamber.
Embodiment 5
Refer to Fig. 2, the utility model provide function described in achievable embodiment 1 or 2 Liquid identification site and Liquid identification device.
It should be noted that Liquid identification site is for positioning or fixing liquid identification device, the utility model is for liquid The structure of body identification device with no restriction, as long as being able to achieve the identification of liquid.It is special such as Publication No. " 105214744A " Liquid sensing device disclosed in benefit application can be used as the Liquid identification device of the utility model, but such liquid sensing dress It is complex to set structure, conductive pin needs to be built into chip interior, and conductive pin is contacted with reaction liquid, in any case It will affect experimental result, and chip preparation difficulty is larger, provides a kind of preferred Liquid identification device in the present embodiment.
In the present embodiment, Liquid identification site includes that light source is raw for positioning Liquid identification device, Liquid identification device At module 28 and photoelectric sensor 29;Liquid identification site includes the upper site for positioned light source generation module 28 and is used for Position the lower site of photoelectric sensor 29, upper site and lower site are respectively arranged on the outside of chip body, upper site, accordingly into Liquid mouth or liquid outlet, the perpendicular line in lower site are successively laid.Correspondingly, light source generation module 28, corresponding inlet or liquid out Mouth, the perpendicular line of photoelectric sensor 29 are successively laid.Since Liquid identification device can be set to liquid quantitative chamber or detection chambers Inlet or liquid outlet at, therefore " corresponding inlet or liquid outlet " herein correspond to liquid quantitative chamber or test chamber The inlet or liquid outlet of room;For example, light source generates mould when Liquid identification device is arranged in the liquid outlet of liquid quantitative chamber Block, the liquid outlet of liquid quantitative chamber, the perpendicular line of photoelectric sensor are successively laid;When the inlet of liquid quantitative chamber is arranged When Liquid identification device, light source generation module, the inlet of liquid quantitative chamber, the perpendicular line of photoelectric sensor are successively laid; When Liquid identification device is arranged in the liquid outlet of detection chambers, light source generation module, the liquid outlet of detection chambers, photoelectric sensor Perpendicular line is 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 can be improved detection efficiency, and then improve quantitative accuracy, while such liquid Body identification device can be set to outside micro-fluidic chip, convenient for being fixed in instrument, without being arranged on chip, reduce chip Difficulty of processing.In use, only light source generation module and photoelectric sensor alignment liquid recognition site need to be placed.Specifically Ground, chip body include 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 function chambers;Light source generation module 28 setting be located in the inlet of liquid quantitative chamber or go out The surface of the corresponding position of the corresponding top plate 1 of liquid mouth, photoelectric sensor 29 be located in the inlet of liquid quantitative chamber or The underface of the corresponding position of the corresponding bottom plate 20 of liquid outlet.
Light source generation module can provide the module of light source, can be LED, halogen lamp, laser lamp etc..In the photograph of light source It penetrates down, since gas, liquid are to the transmissivity and refractive index difference of light, the light intensity for being irradiated to photoelectric sensor is different, photoelectricity Inductor can identify gas and liquid, to distinguish whether liquid arrives the point of induction., when liquid flow to inlet or goes out When liquid mouth, Liquid identification device can be identified quickly, to control liquid driving device.
Embodiment 6
The embodiments of the present invention additionally provide a kind of analysis instrument with micro-fluidic chip comprising instrument frame Micro-fluidic chip in frame, at least one reagent storage pool, liquid driving device, detection device and any of the above embodiment;Its In, micro-fluidic chip is mounted in the apparatus frame;The liquid driven power entrance phase of liquid driving device and micro-fluidic chip Even;Reagent storage pool can be connected to on-off with corresponding reagent inlet;Detection device is issued for receiving processing micro-fluidic chip Detection signal.
Optionally, the liquid driving device is plunger pump;It is equipped on each reagent storage pool and outside air The opening of connection.
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 (15)

1. a kind of micro-fluidic chip, which is characterized in that including chip body and the sample introduction being arranged in the chip body Mouth, air intake, liquid driven power entrance, air subchannel, main fluid passageway and multiple function chambers;The main fluid passageway It is connected to the multiple function chamber, the liquid driven power entrance is for connecting liquid driving device to drive liquid in the master It is flowed in fluid channel and multiple function chambers;
At least one of the multiple function chamber is liquid quantitative chamber, and the liquid quantitative chamber has scheduled appearance Product, and is provided with Liquid identification site at the liquid outlet of liquid quantitative chamber, need to liquid quantitatively from the liquid quantitative chamber The inlet of room flows into the liquid quantitative chamber, full of reaching the liquid outlet after the liquid quantitative chamber;
The liquid quantitative chamber includes sample amounts chamber, and fluid sample flows into the sample amounts chamber through the injection port It is quantified;One end of the air subchannel is connected to the air intake, the other end and the sample amounts chamber and institute The main fluid passageway connection between injection port is stated, the other end of the air subchannel and the connectivity part of the main fluid passageway are adjacent The nearly sample amounts chamber.
2. micro-fluidic chip according to claim 1, which is characterized in that the liquid driving device is plunger pump.
3. micro-fluidic chip according to claim 1, which is characterized in that be provided with liquid at the inlet of liquid quantitative chamber Body recognition site.
4. micro-fluidic chip according to claim 1, which is characterized in that the liquid quantitative chamber further includes reagent quantitative The inlet of chamber, the reagent quantitative chamber is connected to one end of reagent subchannel, the other end of the reagent subchannel with Reagent inlet connection, the reagent quantitative chamber are set to the downstream of the sample amounts chamber.
5. micro-fluidic chip according to claim 1, which is characterized in that the function chamber includes detection chambers, described Detection chambers have scheduled volume, and Liquid identification site is provided at the liquid outlet of the detection chambers, to be detected Liquid flows into the detection chambers through the inlet of the detection chambers, full of reaching liquid outlet after the detection chambers.
6. micro-fluidic chip according to claim 5, which is characterized in that be also equipped at the inlet of the detection chambers Liquid identification site.
7. micro-fluidic chip described according to claim 1~any one of 6, which is characterized in that use in the Liquid identification site In positioning Liquid identification device;The Liquid identification device includes light source generation module and photoelectric sensor;
The Liquid identification site includes upper site for positioning the light source generation module and for positioning the light inductance The lower site of device is answered, the chip body includes top plate and bottom plate, and the upper site and the lower site are respectively arranged on the top The outside of plate and the bottom plate, the position and corresponding liquid outlet or inlet in the upper site and lower site are corresponding, so that The light source generation module, corresponding liquid outlet or inlet, the perpendicular line of the photoelectric sensor after must positioning successively cloth If.
8. micro-fluidic chip according to claim 1, which is characterized in that the liquid quantitative chamber is hexagonal structure Chamber.
9. micro-fluidic chip according to claim 5, which is characterized in that the width of the inlet of the liquid quantitative chamber It is highly 0.3-3mm for 0.3-3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3-3mm, is highly 0.3- 3mm;Or
The surface of the liquid quantitative chamber is the surface formed after hydrophilic surface is modified;The liquid quantitative chamber The width of inlet is 0.3-5mm, is highly 0.3-3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3-5mm, Height is 0.3-3mm;Or
The surface of the liquid quantitative chamber is the surface formed after hydrophobic surface is modified, the liquid quantitative chamber The width of inlet is 0.3-2mm, is highly 0.3-3mm;The width of the liquid outlet of the liquid quantitative chamber is 0.3-2mm, Height is 0.3-3mm.
10. micro-fluidic chip according to claim 1, which is characterized in that the chip body includes top plate and bottom plate;Institute It states top plate and bottom plate stacking connects;The junction of the top plate and the bottom plate is provided with the main fluid passageway and described Multiple function chambers.
11. micro-fluidic chip according to claim 10, which is characterized in that the bottom plate is smooth plate, the top Micropore, microchannel or microcavity body are provided on plate to form the injection port, liquid driven power entrance, main fluid with the bottom plate Channel or function chamber.
12. micro-fluidic chip according to claim 1, which is characterized in that the injection port and the sample amounts chamber Between be equipped with Whole Blood Filtration chamber, whole blood filter membrane is equipped in the Whole Blood Filtration chamber.
13. a kind of analysis instrument containing micro-fluidic chip, which is characterized in that including apparatus frame, liquid driving device, detection dress It sets and micro-fluidic chip described in claim 1;Wherein, the micro-fluidic chip is mounted in the apparatus frame;The liquid Body drive is connected with the liquid driven power entrance of the micro-fluidic chip;The detection device is described micro- for receiving processing The detection signal that fluidic chip issues.
14. the analysis instrument according to claim 13 containing micro-fluidic chip, which is characterized in that the micro-fluidic chip Liquid quantitative chamber further includes reagent quantitative chamber, and the inlet of the reagent quantitative chamber and one end of reagent subchannel connect Logical, the other end of the reagent subchannel is connected to reagent inlet, and the reagent quantitative chamber is set to the sample amounts chamber Downstream;
The analysis instrument further includes reagent storage pool, and the reagent storage pool can be connected to on-off with the reagent inlet.
15. the analysis instrument according to claim 13 containing micro-fluidic chip, which is characterized in that the liquid driving device For plunger pump.
CN201820619055.4U 2018-04-27 2018-04-27 A kind of micro-fluidic chip and the analysis instrument containing it Active CN209549516U (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
CN113115587A (en) * 2019-11-13 2021-07-13 京东方科技集团股份有限公司 Detection chip
CN114981011A (en) * 2019-12-30 2022-08-30 伊鲁米那有限公司 Flow cell assembly and associated reagent selector valve

Cited By (4)

* 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
CN113115587A (en) * 2019-11-13 2021-07-13 京东方科技集团股份有限公司 Detection chip
CN114981011A (en) * 2019-12-30 2022-08-30 伊鲁米那有限公司 Flow cell assembly and associated reagent selector valve
CN114981011B (en) * 2019-12-30 2024-03-29 伊鲁米那有限公司 Flow cell assembly and associated reagent selector valve

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