CN101086504B - Microfluid centrifugal chip and its processing method - Google Patents

Abstract

The invention relates to the making of a micro flow centrifugal chip. It comprises the chip base and cover plate, the base composed of a bended and continuous extending micro slot channel, with the curvature radius ranging 20-1000 micron, at least one inlet at the center of the micro slot channel, at least two outlets at the tail of the micro slot channel. It has a micro slot channel with micro curvature radius spinal, generating clutch acceleration speed to realize the centrifugal operation. It applies to micro processing, being able to realize excellent centrifugal effect, low in cost, and quick.

Description

A kind of microfluid centrifugal chip and job operation thereof

Technical field

The present invention relates to a kind of microfluid centrifugal chip and job operation thereof.

Background technology

Centrifugation technique is to utilize centrifugal force, carry out a kind of technical skill of separating, concentrating and analyzing of material according to the difference of sedimentation coefficient, coefficient of diffusion and the buoyant density of material, in numerous areas such as agricultural, medicine, food hygiene, biological products, bioengineering, cell biology, molecular biology and biological chemistry, obtained using widely, especially the requisite processing links of biological sample preprocessing process.

Along with the development of micro-processing technology, the microchip that is used for clinical examination research has obtained paying attention to widely in recent years.The micro-total analysis system (Micro Total Analysis Systems) that is based upon on the microchip basis becomes analytical chemistry, clinical medicine, biological research focus, and slowly do not break through as centrifugally operated on the sheet of the important component part of sample pretreatment link, this mainly be because still can't realize stablizing at present, gyration parts efficiently.2003, delivered one piece on the Nature and driven in the microcavity of realizing that flows at a high speed eddy current by top cover, and then realized centrifugally operated on the chip article (Nature, 2003,425:38).This chip structure as shown in Figure 1, in this chip, fluid can pass through passage 2 at high speed, thereby the fluid that drives in the microcavity 1 is realized eddy motion at a high speed, because the microcavity yardstick is less, eddy motion at a high speed will be in the very high centrifugal acceleration of the inner generation of eddy current.But the centrifugally operated that top cover driving stream is realized can't be handled the sample of continuous flow, thereby does not have actual centrifugal using value.

Summary of the invention

The purpose of this invention is to provide a kind of micro-fluid chip and job operation thereof.

Microfluid centrifugal chip provided by the present invention comprises the chip matrix and the cover plate that are bonded together, is provided with on described chip matrix:

One has the linear micro-channel of plane curve of bending and continuous deployment characteristics, and the radius-of-curvature of described curve is 20 microns-1000 microns;

At least one import is positioned at the center of micro-channel;

At least two outlets are positioned at the afterbody of micro-channel.

In microfluid centrifugal chip of the present invention, outlet can be set to two at least, lays respectively at the afterbody inboard and the outside of micro-channel.

In microfluid centrifugal chip of the present invention, plane curve commonly used is selected helix for use, is preferably spiral of Archimedes, double curved helix, lituus etc., more preferably spiral of Archimedes.Wherein, the pitch of spiral of Archimedes is that 5 microns-35 microns, micro-channel width are that 10 microns-200 microns, the degree of depth are 10 microns-200 microns.Conventional chip matrix is silicon chip, and cover plate is a glass sheet.

This microfluid centrifugal chip can adopt micro-processing method to be prepared, and comprises the steps:

1) on the chip matrix upper and lower surface, form the layer of silicon dioxide layer with thermal oxidation method, front lighting carve have bending and continuously the plane curve linear graph of deployment characteristics as the mask of subsequent etching;

2) by the photoresist protection, the single face photoetching forms the window of importing and exporting etching, etching, and the position is imported and exported in definition;

3) remove photoresist, press the curvilinear figure etching once more, form conduit;

4), form the passivation layer of conduit at conduit inner surface heat zinc oxide-silicon dioxide layer;

5) with cover plate and chip matrix bonding;

6) at the lower surface deposit silicon carbide layer of chip matrix,, and corrode the formation through hole, promptly obtain described microfluid centrifugal chip in import and exit photoetching.

Microfluid centrifugal chip of the present invention can also adopt other the various micro-processing methods that can realize high-aspect-ratio, closed channel to process, as the mould molding of organic materials such as PDMS, PMMA, photoetching casting (LIGA), glass etching, SU-8 thick resist lithography etc.

Characteristics of the present invention:

1. adopt micro-processing technology to make, have the little and low characteristics of cost of size;

2. employing micro-fluidic technologies, make centrifugal chip of the present invention be convenient to other based on the biological or chemical of micro-fluidic technologies operation carry out integrated on the chip, help developing real chip lab (Lab-on-Chip);

3. pass through to adjust the speed of sample in the chip, or select the turning radius size of microchannel in the chip, can realize the centrifugal acceleration that adjustable extent is bigger.

The principle of work of microfluid centrifugal chip of the present invention is based on sample high-speed motion in having the microchannel of the small turning radius and realizes the centrifugally operated process, different with the centrifugal chip of being delivered on the Nature is: centrifugal chip of the present invention can be realized the continued operation of sample based on the continuous microflow body; In addition, the working flow rate of size by adjusting the microchannel and sample can be realized the centrifugally operated of different centrifugal accelerations.

Microfluid centrifugal chip of the present invention adopts bulk silicon process to make, contain a spiral line type micro-channel, when fluid sample is done high-speed motion in this conduit, because the effect of bending channel with slight curvature radius, will produce centrifugal acceleration, thereby realize centrifugally operated on the sheet.Experimental results show that chip proposed by the invention is suitable for little processing, can realize extraordinary centrifugal effect, have simultaneously that cost is low, speed is fast, be convenient to carry out advantage such as integrated on the sheet with other biological or chemical operation.

Description of drawings

Fig. 1 is the structural representation of the centrifugal chip of existing top cover driving;

Fig. 2 is the front elevation of microfluid centrifugal chip of the present invention;

Fig. 3 is the A-A view of Fig. 2 microfluid centrifugal chip;

Fig. 4 is the process figure of chip center's xsect;

Fig. 5 for microfluid centrifugal chip of the present invention to separation of whole blood figure as a result.

Embodiment

The processing of embodiment 1, microfluid centrifugal chip:

Microfluid centrifugal chip structure of the present invention as shown in Figures 2 and 3, wherein, Fig. 3 is the A-A cut-open view of Fig. 2.This chip mainly comprises and is etched on the silicon chip 7, and by the spiral line type micro-channel 6 of cover glass 8 sealings (treat centrifuged sample move therein); The import 3 at helical duct center is used for sample feeding; Chip comprises two outlets, and outer side outlet 4 and interior side outlet 5 are used to extract the sample behind the centrifugally operated.The thickness of silicon chip 7 is 400 μ m; Cover glass 8 thickness are 500 μ m; The width of spiral line type micro-channel 6 is 120 μ m, and the degree of depth is 60 μ m, and the pitch of Archimedes's (spiral line type of present embodiment) helix is 23 μ m, and spiral lay is changed to 37 π from 4 π; Import 3, outer side outlet 4 and interior side outlet 5 all are through holes, its cross section flare, port width is 568 μ m, the diameter of through hole is 100 μ m.

This microfluid centrifugal chip adopts the silicon micro-processing method to realize the process of chip center's xsect such as Fig. 4:

At first, forming a bed thickness in silicon chip 9 upper and lower surfaces with thermal oxidation process is 6000

Silicon dioxide layer, and carve the etching figure at front lighting, make its mask that becomes micro-channel 9 (Fig. 4-a); By the photoresist protection, and the window 10 of single face photoetching formation import and export etching (Fig. 4-b); ICP etch silicon 40 μ m, remove photoresist (Fig. 4-c); 60 microns of ICP etchings are removed pros and cons silicon dioxide layer (Fig. 4-d); Thermal oxide 1500

Silicon dioxide layer forms the passivation layer 11 of vias inner walls, removes the silicon dioxide layer (Fig. 4-e) at the back side by RIE; Carry out silicon-glass anode linkage (surface channel and glass 8 bondings), and formation glass carrier and complete micro-channel (Fig. 4-f); Opposite side silicon substrate surface deposit PECVD silicon carbide layer 12, and the window of photoetching formation corrosion perforate, and by KOH corrosion formation through hole (Fig. 4-g), promptly obtain microfluid centrifugal chip.

Use this microfluid centrifugal chip blood is carried out the microfluid centrifugal operation, centrifugal back leukocyte count and RBC number outside in the side outlet 4/ ratio of side outlet 5 with the variation diagram of driving pressure differential (among the figure, the different different batches experimental results that are labeled as) as shown in Figure 5.

The result shows that this microfluid centrifugal chip can produce the centrifugal acceleration that is 2000g to the maximum under the driving pressure differential of 0.7MPa, and can well leucocyte concentration and separation from whole blood be come out.The ratio of the quantity of leucocyte of outer side outlet and interior side outlet quantity of leucocyte is much larger than 1, and this shows that this microfluid centrifugal chip can realize centrifugally operated preferably.

Claims (5)

1. a microfluid centrifugal chip comprises the chip matrix and the cover plate that are bonded together, is provided with on described chip matrix:

One has the linear micro-channel of plane curve of bending and continuous deployment characteristics, and the radius-of-curvature of described curve is 20 microns-1000 microns;

At least one import is positioned at the center of micro-channel;

At least two outlets are positioned at the afterbody of micro-channel;

Described have bending and continuously the plane curve of deployment characteristics is linear for spiral yarn shaped; Described spiral yarn shaped be spiral of Archimedes; The pitch of described spiral of Archimedes is 5 microns-35 microns, and the micro-channel width is 10 microns-200 microns, and the degree of depth is 10 microns-200 microns.

2. microfluid centrifugal chip according to claim 1 is characterized in that: described outlet is two.

3. microfluid centrifugal chip according to claim 1 is characterized in that: the cross section of described import and outlet is toroidal.

4. according to the arbitrary described microfluid centrifugal chip of claim 1-3, it is characterized in that: described chip matrix and cover plate are silicon chip and/or glass sheet.

5. the job operation of the described microfluid centrifugal chip of claim 1 comprises the steps:

1) on the chip matrix upper and lower surface, form the layer of silicon dioxide layer with thermal oxidation method, front lighting carve have bending and continuously the plane curve linear graph of deployment characteristics as the mask of subsequent etching;

Described have bending and continuously the plane curve of deployment characteristics is linear for spiral yarn shaped; Described spiral yarn shaped be spiral of Archimedes; The pitch of described spiral of Archimedes is 5 microns-35 microns, and the micro-channel width is 10 microns-200 microns, and the degree of depth is 10 microns-200 microns;

2) by the photoresist protection, the single face photoetching forms the window of importing and exporting etching, etching, and the position is imported and exported in definition;

3) remove photoresist, press the curvilinear figure etching once more, form conduit;

4), form the passivation layer of conduit at conduit inner surface heat zinc oxide-silicon dioxide layer;

5) with cover plate and chip matrix bonding;

6) at the lower surface deposit silicon carbide layer of chip matrix,, and corrode the formation through hole, promptly obtain described microfluid centrifugal chip in import and exit photoetching.

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