CN2559986Y

CN2559986Y - Integrated microfluid and microchip of microarray probe

Info

Publication number: CN2559986Y
Application number: CN 02247727
Authority: CN
Inventors: 温龙平; 唐飞; 连崑
Original assignee: Bosheng Weijing Science & Technology Co Ltd Shanghai
Current assignee: Bosheng Weijing Science & Technology Co Ltd Shanghai
Priority date: 2002-08-23
Filing date: 2002-08-23
Publication date: 2003-07-09
Anticipated expiration: 2012-08-23

Abstract

The utility model relates to the microchip of an integration microfluid and a micro array probe, which is characterized in that the microchip comprises a sample cell, a reagent cell, a detection cell, and a microfluid pipe, and each sample cell, reagent cell, and detection cell are connected through each microfluid pipe. The micro array probe is arranged at the bottom of the detection cell. The microchip also comprises a waste liquid cell which is connected with the detection cell through another microfluid pipe. The utility model has excellent parallel detection ability and can realize large amount sample detection at one time, and the utility model also has the function of fast pre-processing and separating sample, thus greatly enhancing the ability of the chip. The utility model is a chip with high integration capacity and strong parallel detection ability, which can reduce the complexity of detection cost and operation. The utility model is applicable to gene, biochemical, and pharmaceutical industries.

Description

The microchip of integrated microfluidic and micro probe array

The utility model belongs to the biochip field, is the microchip of a kind of integrated microfluidic and micro probe array.

Background technology

Current biochip (someone claims microchip) comprises two classes by the action principle branch.

One class is a micro-fluid chip.Micro-fluid chip is also referred to as LAB-ON-CHIP by the mobile detection that reaches various biological components of controlling liquid on chip, promptly finishes breadboard every function on a chip.The control of liquid and various treatment step are realized by make various fine microstructure such as micro-filter, little valve, Micropump, microchannel, little reaction chamber in chip on the micro-fluid chip.Described herein micro-fluid chip just is meant the chip of above-mentioned definition.The characteristics of micro-fluid chip are microminiaturized and integration excellence.So-called microminiaturization is meant that biochemistry detection can carry out in space that dwindles greatly and volume, thereby reduces the consumption of reagent and sample significantly, reduces and detects cost; So-called integration is meant on one chip and realizes detecting required all or most of step (as: processing of sample, separation, reaction and detection).The integration height can make and detect robotization, standardization and unitized, and testing process is operated easily.Micro-fluid chip has excellent performance aspect these two.But a shortcoming of micro-fluid chip is exactly that collimation is relatively poor, that is to say to be conveniently implemented in the sample detection that realizes a greater number on the single chip.This drawbacks limit of micro-fluid chip it detectability and detect flux.

Another kind of chip is a micro-array chip.Micro-array chip is that the chip surface of two dimension or three-dimensional particle surface are divided into many identical zones, and each zone produces a kind of probe and is used for a kind of target molecule of specific detection.Here so-called microarray is meant that identical probe or different probes distribute on chip according to the figure that designs in advance.As shown in Figure 3, this array can be identical or the old formula array of the point of different probe 6, also can be identical or different probe 6A-6F becomes block (Fig. 4), bar shaped (Fig. 5) or probe 6G, 6H, 6J to become the distribution (Fig. 6) of other shape arbitrarily, described herein micro-array chip and microarray just be meant the notion of above-mentioned definition.

The probe of micro-array chip be manufactured with methods such as point sample and original place be synthetic.Concrete process is fixed in biomolecule (oligonucleotide, cDNA, genomic DNA, polypeptide, antigen, antibody etc.) exactly and forms the biomolecule dot matrix on the solid-phase medias such as silicon chip, glass sheet.The biomolecule in sample to be analyzed and the probe molecule of biochip utilize scanner that hybridization signal is detected and analyzes after hybridization or interaction take place.Present most widely used micro-array chip is a genetic chip, and it adopts OLIGO or dna segment is probe, detects DNA or mRNA.Micro-array chip has microminiaturized advantage.The very important advantage of it another is exactly the collimation excellence, that is to say that it can be on single chip realizes the detection of a lot of target molecules or sample simultaneously, thereby can realize high throughput testing.For example the dot matrix number of the chip gene expression profile of Affymetrix company development can reach 400,000 points.But very difficult job step before the analyses such as The pretreatment is integrated on the chip of micro-array chip finished, and can only rely on artificial or special instrument to realize these steps, the integration that is to say it is bad, thereby great amount of manpower and material resources have been wasted, and the system automation degree is not high, is not easy standardization.If micro-array chip and micro-fluid chip are realized on same chip, just can take into account the characteristics of two kinds of chips, realize having complementary advantages, guaranteeing on the microminiaturized basis, reach huge collimation and excellent integration simultaneously.Do not see at present the report of this integrated chip.

Content of the present utility model

Present situation and above-mentioned analysis at present biochip exploitation, the purpose of this utility model is exactly that function with micro-fluid chip and micro-array chip integrates, realize a kind of height integration that had both had micro-fluid chip, have the novel chip and the method for the characteristics of the powerful parallel detection ability of micro-array chip again.

The purpose of this utility model is achieved through the following technical solutions, the microchip of a kind of integrated microfluidic of the utility model and micro probe array, it is characterized in that: have reagent pond and microfluid pipeline on described microchip, each reagent pond links to each other by each microfluid pipeline.In order to express conveniently, the cavity of depositing reagent, sample or mixed liquor is referred to as the reagent pond.In described each reagent pond, has micro probe array on the bottom in one or several reagent pond.The reagent pond of above-mentioned band micro probe array is called detection cell again.Described reagent pond also can comprise sample cell and waste liquid pool, and described waste liquid pool can link to each other with detection cell through another microfluid pipeline.The utility model is when being used for detecting application, and it detects step and is exemplified below:

Sample at first is injected in the sample cell, flows into detection cell by sample cell then.In detection cell, the micro probe array of sample and detection cell bottom reacts, and after reaction was finished, waste liquid flowed into waste liquid pool; Then, all ingredients respectively from reagent pond separately order flow into detection cell, reactant is cleaned or reacts.Every kind of reagent fully is being discharged into waste liquid pool after cleaning or the reaction.Afterwards, with optics or other pick-up unit the reactant in the detection cell is detected.Whole process only need be injected sample (may also comprise reagent), and remaining whole operations are all finished on chip automatically.The sample of present micro-array chip need carry out outside pre-service earlier, could detect with micro-array chip then, and various preprocessing process all is to finish by manual or other specialized equipment.In the utility model chip, then do not need these outside pre-treatment step, outside pre-treatment step originally now fully or major part can on the utility model chip, carry out.In existing micro-fluid chip, generally have only a kind of probe or reactant in the detection cell, also can only detect a kind of sample or a kind of composition, and in the utility model chip, owing to made the array of microprobe in the bottom of detection cell, so can detect the multiple composition of several samples or sample simultaneously.Thereby the function of the utility model chip is more comprehensive.

In sum, advantage of the present utility model mainly contains:

1. compare with present micro-fluid chip: owing to made micro probe array in the test chamber, this

The utility model chip has more excellent parallel detection ability, than existing microfluid core

The sheet sensing range is more powerful, once can realize the detection of big figure sample;

2. compare with existing micro-array chip: since integrated have the quick sample pre-treatment and

The ability of the micro-fluid chip of separation function, the utility model chip does not need additionally

, the sample pre-treatments and the mask work of complicated, labor intensive and material resources, greatly

Improved the function of chip, the cost that has reduced detection and the complicacy of operation, thereby

The automaticity of system is higher, is easier to standardization.

Description of drawings

Fig. 1 is the synoptic diagram of the utility model microchip,

Fig. 2 is operating position figure of the present utility model,

Fig. 3-6 is the probe microarray synoptic diagram of different shape.

Code name explanation I chip I I turntable 1 detection cell 2 waste liquid pools 3 microchannels 4 reagent ponds 5 sample cells 6,6A-6J

micro probe array

7,8 microchannels among the figure

Embodiment

The method of utilizing LIGA technology and micro-array chip manufacture craft to combine is made microfluid and the integrated chip of microarray on PMMA.Be manufactured with micro probe array in the detection cell of this chip, can carry out the detection of a plurality of samples simultaneously, another independent patent that the making of chip adopts us to apply for is made; The drive principle of liquid adopts the centrifugal force method of driving in the chip.About the microfluidic control system of this centrifugal force, we have applied for another independently patent of invention technology; The detection system of chip has also been applied for another independently patent of invention; The structure of chip I as shown in Figure 1.As Fig. 1, on the utility model chip I, have sample cell 5, reagent pond 4, detection cell 1, waste liquid pool 2 and each

microchannel

3,7,8, each reagent pond 4 links to each other with sample cell 5 by each microchannel 3, sample cell 5 links to each other with detection cell 1 through microchannel 7, has micro probe array 6 in the bottom of detection cell 1, can carry out the detection of a plurality of samples simultaneously, interlink through microchannel 8 and waste liquid pool 2 at an end of detection cell 1.As Fig. 2, this chip I can be placed on the turntable II, around the rotation of its center O with regulate the angle θ of this chip I, make the capillary resistance of centrifugal force F by turntable II greater than pipeline around the axle center O ' rotation of oneself, liquid is delivered to another pond from a pond.

The course of work of chip I is as follows:

All ingredients is stored in separately the reagent pond 4 in advance.

During detection, at first testing sample is splashed into sample cell 5; Under the effect of centrifugal force F, sample flows into the micro probe array 6 of detection cell 1 bottom detection cell through microchannel 7 and reacts;

Behind the sufficient reacting, by the control of centrifugal force, sample flows into waste liquid pool 2 through microchannel 8;

Utilize centrifugal force, microfluidic control system is cleaned or is reacted by making different reagent enter 1 pair of probe of detection cell from separately reagent pond 4 order, clean or sufficient reacting after, waste liquid flows into waste liquid pools 2 through microchannel 8;

After above-mentioned preprocessing process and reaction are finished, utilize detection system that the micro probe array in the detection cell 6 is detected, qualitative or quantitatively determine the composition of sample.

Claims

1, the microchip of a kind of integrated microfluidic and micro probe array is characterized in that: have reagent pond and microfluid pipeline on described microchip, each reagent pond links to each other by each microfluid pipeline; In described each reagent pond, has array probe on the bottom in one or several reagent pond.

2, the microchip of integrated microfluidic according to claim 1 and micro probe array is characterized in that: described reagent pond also comprises sample cell, waste liquid pool.