CN202315775U

CN202315775U - Micro hybrid device

Info

Publication number: CN202315775U
Application number: CN2011204316842U
Authority: CN
Inventors: 刘笔锋; 李颖; 徐友志; 冯晓均
Original assignee: Huazhong University of Science and Technology
Current assignee: Huazhong University of Science and Technology
Priority date: 2011-11-04
Filing date: 2011-11-04
Publication date: 2012-07-11
Anticipated expiration: 2021-11-04

Abstract

The utility model discloses a fast micro hybrid device for high-viscosity solution, which comprises a thin polydimethylsiloxane (PDMS) layer. The fast micro hybrid device is characterized in that three communicated channels are arranged on the thin PDMS layer, two solution inlet channels are symmetric with respect to a third solution outlet channel, a plurality of omega-shaped micro structures are sequentially arranged in the solution outlet channel, and two openings of each omega-shaped micro structure face the crossed positions of the three channels. The fast micro hybrid device is simple in structure and easy in processing process and enables the high-viscosity solution to be completely mixed within 500 mus.

Description

A kind of micro mixing device

Technical field

The utility model relates to a kind of quick micro mixing device that is used for high viscosity solution, can high viscosity samples solution be realized the mixing of microsecond level, is widely used in the dynamics research field of large biological molecules such as protein or DNA under crowded environment.

Background technology

The micro-fluidic chip laboratory is important science and technology in this century; It is characterized by a biological or chemical laboratory micro to a piece is had only on several square centimeters the thin slice; It realizes the integrated of sequence of operations unit such as sample introduction, preliminary treatment, mixing, reaction, detection through structures such as microchannel, little valve and Micropumps; The superintegrated small platform in this multi-functional unit makes the sample treatment time significantly shorten, and detection resolution significantly improves.At present, micro-fluidic chip has been applied to comprise that medical diagnosis on disease, environmental monitoring, food security etc. and people live among closely bound up numerous industries.

Micro-mixer is as a pith in the micro-fluidic chip; It can realize that chemistry or biological sample fast and effectively mix; And the examination amount that consumes do not receiving upgrading not; Be beneficial to very much valuable biological samples such as analysing protein or nucleic acid, be considered to study an effective tool of quick bio chemical reaction.

Protein is one type of very important big molecule in the cell, and it is as the executor of vital movement, and its folding mechanism is a still unsolved great biological question in the molecular biology central dogma.For a long time, because some actual cause, the experiment that the research aleuroplast folds outward is generally in some simple buffer systems---carry out in the weak solution.Yet all exist various large biological molecules such as amounts of protein, nucleic acid, polysaccharide in all cells; They approximately take 20%～30% of cell volume; Total concentration is full of in other macromolecular crowded environment so any big molecule all is in one up to 80～200g/L.Therefore; Research to protein folding need be considered " big molecule crowding effect " (A.P.; Minton; The effect of volume occupancy upon the thermodynamic activity of proteins:some biochemical consequences.Mol Cell Biochem, 1983,55 (1): 119～140).For the folding power of research protein under crowded environment learned situation; The researcher is dissolved in the solution (this solution viscosity is high) with congestion state (M.Smita, and M.W., the Matthias of simulated albumin matter in cell with the bovine serum albumin of high concentration or ficoll or polyethylene glycol; (2009) Effect of Macromolecular Crowding on Protein Folding Dynamics at the Secondary Structure Level; J.Mol.Biol., 393,227-236).

For in micro-fluidic chip, realizing the mixing of high viscosity solution; People such as Xia (H.M.; Xia and Z.P.Wang, (2010) A microfluidic mixer with self-excited ' turbulent ' fluid motion for wide viscosity ratio applications, lab chip; 10; 1712-1716) designed a double-deck chip,, brought violent disturbance to realize the mixing of high viscosity solution thereby make solution constantly get into big chamber suddenly by capacitor through solution flowing in the middle of up and down two-layer passage.This device can be realized the mixing of two kinds of solution that viscosity differences is very big, but its incorporation time long (being about 1min), and its chip is double-decker, and processing is comparatively complicated.People such as Wang (S.S.; Wang and X.Y.; Huang (2011) Mixing enhancement for high viscous fluids in a microfluidic chamber, lab chip, 11; 2081-2087), make full-bodied glycerite realize rapid mixing through in the hybrid chamber of microchip, adding the piezoelectricity dingus of a dither.The incorporation time of this micro-mixer is about 5s, the disturbance of its solution need additionaling power device (piezo-electric device) thus effect make its overall structure seem comparatively complicated.

The utility model content

The purpose of the utility model is to overcome existing high viscosity solution micro mixing device complex structure, and the shortcoming that incorporation time is long provides a kind of simple in structure, processing is simple and easy, incorporation time is short micro mixing device.

A kind of quick micro mixing device that is used for high viscosity solution; Comprise the PDMS thin layer; Be processed with three passages that are connected on the said PDMS thin layer; Wherein two solution access roades are about the 3rd taphole passage symmetry, and order is processed with a plurality of ω type micro-structurals in the taphole passage, and two openings of ω type micro-structural are towards the triple channel infall.

Further, the difference in size of said a plurality of its left and right sides openings of sizes of ω type micro-structural alternately on the occasion of and negative value.

Further, be partial to taphole passage left side and right side respectively near two ω type micro-structurals of triple channel infall.

Further, also comprise the substrate that has sample holes.

Further, also comprise the chip gripper that is used to introduce external solution.

The outstanding feature of the utility model is: (1) has proposed a kind of asymmetric ω structure of breaking solution layer stream mode in the microchannel, thereby reaches rapid mixing (about 500 μ s) through the high viscosity solution in the effective disturbance passage of ω structure that will put in the cycle; (2) with the chip gripper ways of connecting external solution is introduced chip again through punching on substrate; With traditional dimethyl silicone polymer (PDMS) go up punching be connected again the sample introduction pipe mode compare; The utility model more economical convenience that seems, and can reduce of the pollution of PDMS chip to the microchannel.This device provides a kind of new approach for research protein or DNA in folding power down of big molecule congestion state, in that the rapid mixing and the reaction field of high viscosity solution are with a wide range of applications from now on.

Description of drawings

Fig. 1 MCA sketch map.

Fig. 2 micro-mixer assembling sketch map.

The mixing resultant figure of the aqueous solution under different flow in Fig. 3 micro-mixer; Mixed effect figure when Fig. 3 (a)-(d) is respectively 0.003mL/min, 0.03mL/min, 0.1mL/min, 0.22mL/min flow; Fig. 3 (e) is the fluorescence distribution of position shown in Fig. 3 under the different flow (a) dotted line, and Fig. 3 (f) is the mixing efficiency sketch map under the different flow.

The mixing resultant figure of HEC in Fig. 4 micro-mixer, the mixed effect figure when Fig. 4 (a) is the 0.25mL/min flow, the mixing efficiency sketch map of position shown in the dotted line among Fig. 4 (a) when Fig. 4 (b) is the 0.25mL/min flow.

The mixing resultant figure of glycerine in the micro-mixer under Fig. 5 different flow, Fig. 5 (a) are 50% glycerine and water mixing resultant sketch map, and Fig. 5 (b) is 50% glycerine and 50% glycerine mixing resultant sketch map.

The specific embodiment

Below in conjunction with accompanying drawing and instance the utility model is done detailed explanation.

Fast micro mixing device comprises the PDMS thin layer, is processed with three passages that are connected on the said PDMS thin layer, two solution access road a wherein, and b is about the 3rd taphole passage c symmetry, and order is processed with a plurality of ω type micro-structurals in the taphole passage.The triple channel connected mode can take to be Y type, T type or arrowhead-shaped that two openings of ω type micro-structural are towards the triple channel infall.As optimization, the arrangement mode of ω type micro-structural in passage be its left and right sides openings of sizes difference in size alternately on the occasion of and negative value.This mode with merely the mode of ω type micro-structural forth in passage compared, can more effectively cause the disturbance of solution, the experiment rapid mixing.Simultaneously, with being partial to taphole passage left side and right side respectively near two ω type micro-structurals in triple channel crosspoint, two solution are extruded in the littler space when just getting into exit passageway, final realization mixes of great advantage fully to solution.

In order to introduce external solution, traditional approach is generally taked punching back bonding slide on the PDMS thin layer, connects the mode of draw point and plastic tube again in PDMS punching place.Thereby this mode brings the PDMS chip to block the microchannel on the one hand easily; On the other hand PDMS punching place bond strength relatively a little less than, the flow of solution of high flow rate is out-of-date will be washed open easily here.For overcoming the problems referred to above, the utility model is taked earlier substrate accurately to be punched, then with PDMS thin layer bonding, and the last introducing that with the chip gripper that is connected with draw point and plastic tube the mode of PDMS chip encapsulation is realized external solution again.

Fig. 1 has provided an instance; Be processed with T type passage in the instance on the PDMS thin layer, two access road width are 200 μ m, and narrow its width of position is 20 μ m in the exit passageway; Its width of wide position is 200 μ m; Exit passageway is processed with 7 ω type micro-structurals, according to the positive mode in the negative earlier back of the difference in size of left and right sides openings of sizes arrange be sequence number be its left opening of ω type micro-structural of 1,3,5,7 less than right opening, sequence number is that its left opening of ω type micro-structural of 2,4,6 is greater than right opening; And the 1st ω type micro-structural deflection taphole passage left side, the 2nd ω type micro-structural deflection taphole passage right side.

The instance that Fig. 2 provides is the assembling process of said micro mixing device.

The specific embodiment of micro mixing device is following:

1.PDMS the preparation of thin layer: at first make the SU-8 formpiston with soft lithography.Be about to SU-8 (1070) and get rid of on the silicon chip of cleaning oven dry (700r 18s, 2100r 60s), (65 ℃ of 15min, 95 ℃ of 40min) after the solvent in the SU-8 glue are removed in preceding baking, carry out photoetching (40s, 3.5mJ/cm ²), place then and carry out back baking (65 ℃ of 15min, 95 ℃ of 40min) on the flat plate heat; Behind developing liquid developing, carry out post bake (135 ℃ of 120min) more afterwards, get final product the formpiston of tool micro-structural (according to picture that Electronic Speculum is clapped; Measure its highly about 27 μ m), its passage concrete structure figure one.After producing formpiston, copy on the PDMS with the micro-structural of quick molding method again formpiston.Be about to PDMS and its curing agent and obtain preceding aggressiveness by 10: 1 mixings and degasification, then aggressiveness before the PDMS is fallen on formpiston, 65 degree curing are 4 hours on the flat plate heat, the PDMS thin layer (thick about 3cm) that the PDMS after the curing is uncovered and cuts edge and can obtain containing the microchannel.

2. the accurate punching of substrate.It is gluing good with 502 with the common slide of 1mm (sacrifice layer) that 3mm is thickeied slide (substrate), places then (substrate is last) on the miniature numerical control lathe.Related software through Digit Control Machine Tool reads the autocad file that contains three sample holes in microchannel, and has established relevant parameter, and slide is accurately punched.Have openning hole the back with acetone, Piranha solution (dense H ₂SO ₄: H ₂O ₂=3: 1, v/v), after ultra-pure water cleans, oven dry obtains clean substrate on flat plate heat.

3.PDMS bonding with substrate.The PDMS thin layer that will contain the microchannel and the clean substrate that contains sample holes are as for handling (800V in the plasma clean device; 2min); Drip water yield ultra-pure water at bonding face; Under vertical microscope, three sample holes on the PDMS thin layer are accurately aimed at three holes on the glass substrate then, place vacuum drying oven then, under vacuum state, obtain the PDMS chip behind 65 ℃ of heating 2h.

4.PDMS the assembling of chip and chip gripper.After obtaining the PDMS chip, for extraneous solution is imported in the chip, need the micro-mixer device that assembles itself and chip gripper to the end, it is assembled, and sketch map is as shown in Figure 2, and wherein a is a sample introduction pipe one, and its material is a polyfluortetraethylene pipe; B is a sample introduction pipe two, and its material is a polyfluortetraethylene pipe; C is the taphole pipe, and its material is a polyfluortetraethylene pipe; D, e, f are stainless steel tube; G is a fixed screw; H is the chip gripper cover plate, and its material is the thick lucite of 8mm; I is a seal washer, and its material is a silicon rubber; J is a substrate, and its material is for carrying fragmentation; K is the PDMS that contains the microchannel; L is the chip gripper egative film, and its material is the thick corrosion resistant plate of 3mm.

After the assembling of micro-mixer device was accomplished, we used the sample of the aqueous solution of fluorescein and sulphonyl rhodamine as the preliminary assessment mixed effect earlier.Under different flow, with micro syringe pump two solution are injected from two inlets with identical speed, its mixed effect is seen Fig. 3.

For studying the mixed effect of this micro mixing device to high viscosity solution, we feed 1% hydroxyethylcellulose (HEC) respectively with the aqueous solution from two inlets of two micro-mixers, and when two inlet flow rates were 0.25mL/min, its mixed effect was as shown in Figure 4.

Attach: 2% HEC collocation method: 100mL water is heated to 80 ° and keep this temperature, while stirring 2g HEC is added then and be mixed with 2%HEC in the entry, its theoretical viscosity is about 4000cp, as required HEC is diluted with water to corresponding viscosity.

For further studying the mixed effect of this micro mixing device to high viscosity solution; We feed two inlets of blender respectively with the glycerine of the glycerine of the glycerine of (a) 50% and water, (b) 50% and 50%, under the different flow at the mixer outlet place its mixing efficiency as shown in Figure 5.

Claims

1. quick micro mixing device that is used for high viscosity solution; Comprise the PDMS thin layer; It is characterized in that, be processed with three passages that are connected on the said PDMS thin layer, wherein two solution access roades are about the 3rd taphole passage symmetry; Order is processed with a plurality of ω type micro-structurals in the taphole passage, and two openings of ω type micro-structural are towards the triple channel infall.

2. quick micro mixing device according to claim 1 is characterized in that, the difference in size of said a plurality of its left and right sides openings of sizes of ω type micro-structural alternately on the occasion of and negative value.

3. quick micro mixing device according to claim 1 is characterized in that, is partial to taphole passage left side and right side respectively near two ω type micro-structurals of triple channel infall.

4. quick micro mixing device according to claim 1 is characterized in that, also comprises the substrate that has sample holes.

5. quick micro mixing device according to claim 4 is characterized in that, also comprises the chip gripper that is used to introduce external solution.