CN101717068B - Method for preparing polymeric micro-fluidic chip based on hydrogel male mold - Google Patents
Method for preparing polymeric micro-fluidic chip based on hydrogel male mold Download PDFInfo
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Abstract
The invention relates to a method for preparing a polymeric micro-fluidic chip based on a hydrogen male mold, which comprises the following steps: transferring a micro-fluidic channel structure of the micro-fluidic chip arranged on a mask into a photoresist layer (9) in an etching way to obtain a photoresist female mold (11); heating and melting agar hydrogel or gelatin hydrogel (8) and pouring the melted hydrogel (8) on the photoresist female mold (11); covering the hair side of a frosted glass plate (12) on the melted hydrogel (8) and pressing the hair side down; after the hydrogel is solidified, separating the solidified hydrogel together with the frosted glass plate (12) from the photoresist female mold (11) to obtain the hydrogel male mold (13); mixing a macromolecular polymer and a curing agent to obtain a casting solution (14); pouring the casting solution (14) on the hydrogel male mold (13) and covering a cover plate (15) over the hydrogel male mold (13) so that a gap between the cover plate (15) and the hydrogel male mold (13) is filled with the casting solution (14); performing mold stripping after the casting solution (14) is solidified at a room temperature to obtain a substrate (16) of the polymeric micro-fluidic chip; and encapsulating the substrate (16) with a cover piece to obtain the finished product (18) of the polymeric micro-fluidic chip. The method can be used for machining the polymeric micro-fluidic chips made from polymethylmethacrylate, dimethyl silicone polymer, epoxy resin and the like.
Description
Technical field
The invention belongs to the micro-fluidic chip technical field, be specifically related to a kind of method for preparing polymeric micro-fluidic chip based on hydrogel male mold.
Background technology
Micro-fluidic chip in nineteen ninety by Manz and Widmer[1] propose first, be the micro-full analytical system (important component part of μ-TAS).As a kind of emerging differential compartment analysis technology, in the short more than ten years, developed into one of scientific and technological research field of forefront on the our times.This technology relates to analytical chemistry, material science, electronics, the micro-electro-mechanical systems subjects such as life science of unifying, and is a highly integrated technical system.As a frontier interdisciplinary, its target is to realize that by micro electronmechanical processing (MEMS) technology and biotechnology chemical analysis system from sample pretreating to whole microminiaturized, the integrated and portability that detects, is important directions and the forward position of present analysis Instrument Development.Micro-fluidic chip is take the microchannel network as architectural feature, it is the emphasis of current micro-total analysis system development, and efficient with it, fast, few, the low consumption of reagent dosage and integrated level advantages of higher caused domestic and international analysis and life science circle relevant expert's extensive concern, shown good application prospect in environmental monitoring, clinical diagnosis, Pharmaceutical Analysis, legal medical expert and the field such as military, various new micro-flow control chip preparation methods emerge in an endless stream [2].
The rapidoprint of micro-fluidic chip mainly comprises glass and various polymer [3], the early stage glass-chip that mostly is that uses of studying, its process technology requires high, need special-purpose equipment, and every chip need carry out separately photoetching and chemical attack, be difficult to adopt mould to be produced in enormous quantities, price comparison is expensive, has limited its application.So, polymer is developed by chip in recent years, it makes the main technology such as injection moulding, die, casting and monomer injection molding in-situ polymerization that adopt, because cheap and easy production in enormous quantities, has good industrialization prospect, wherein polymethyl methacrylate (lucite) and dimethyl silicone polymer (silicon rubber) are two kinds of polymer [4,5] commonly used in the facture of microchip.Usually polymethyl methacrylate micro flow control chip adopts the molded standby technology of hot padding, namely under the condition that is higher than polymethyl methacrylate vitrification point (105 ℃), make the structure replication of anode membrane to the polymethyl methacrylate plate by exerting pressure, and dimethyl silicone polymer micro flow control chip use casting method more.Rigid die is used in the at present processing of polymeric micro-fluidic chip more, such as the photoresist anode membrane on silicon formpiston, metal anode membrane and the silicon chip, need to adopt micro electronmechanical process technology, cost of manufacture is high, and step is many, and every formpiston needs separately processing, especially when casting method prepares polymeric micro-fluidic chip, active force is larger between the polymeric micro-fluidic chip of silicon and metal and shaping, and the demoulding is very difficult, often causes the damage of mould and chip.So the easy demoulding formpiston of the processing energy batch low-cost production that uses cheap materials is significant.
We find that various hydrogels have good mechanical strength in correlative study, hot reversible hydrogel particularly, be heated under the uniform temperature and can be molten into solution, be cooled to uniform temperature and can be cured as gel, can pass through the fusion-cast batch duplicating, good application prospect is arranged in the processing of micro-fluidic chip formpiston, but through consulting domestic and foreign literature, there is not yet the report that uses hydrogel male mold processable polymer micro-fluidic chip.Hydrogel is flexible die, and the easily demoulding is hydrophilic material because containing a large amount of moisture, and is immiscible with hydrophobic macromolecule prepolymer injection molded material, can be used for casting method processable polymer micro-fluidic chip.The present invention has set up a kind of method for preparing polymeric micro-fluidic chip based on the reversible hydrogel male mold of elastic hot, has advantages of that technique is simple and with low cost.Hydrogel male mold easily by fusion-cast method batch duplicating, can repeatedly use and melt recovery, in the low-cost processing of the batch of polymeric micro-fluidic chip good application prospect is arranged.Prior art related to the present invention has:
[1]Manz?A，Graber?N，Widmer?HM.Sens.Actuators?B?1990，1，244-248.
[2]Dittrich，P.S.，Tachikawa，K.，Manz，A.，Anal.Chem.2006，78，3887-3908.
[3]Verpoorte?E.Electrophoesis?2002，23，677-712.
[4]Becker?H，Locascio，L.E.Talanta?2002，56，267-287.
[5]Becker?H，Gartner?C.Electrophoesis?2000，21，12-26.
Summary of the invention
The object of the invention is to propose a kind of method for preparing polymeric micro-fluidic chip based on hydrogel male mold.
The present invention will transfer to hydrogel surface by the micro-fluidic chip microchannel structure (such as accompanying drawing 1) on the photoresist former of photoetching technique processing by the method that melting copies, thereby provide elastic hot reversible hydrogel male mold, and the casting method that successfully is used for polymeric micro-fluidic chip is processed, but facilitating chip work flow and reduction chip manufacturing cost are for the low-cost processing of the batch of polymeric micro-fluidic chip provides new technology.
The method for preparing polymeric micro-fluidic chip based on hydrogel male mold that the present invention proposes, concrete steps comprise:
(1) the microchannel structure of the micro-fluidic chip of design on mask can be transferred in the photoresist layer by photoetching, be got the photoresist former;
(2) will be dissolved in the aqueous solution that contains crosslinking agent and plasticizer by heating for agar or the gelatin of preparation hydrogel, get hot reversible hydrogel stamps material after the cooling;
(3) with after agar or the reversible hydrogel stamps material heat fused of gelatin heat, water on the photoresist former, and the hair side of frosted glass plate is covered on the hydrogel of fusing, after its cooled and solidified, it can be separated with the photoresist former together with frosted glass plate, get hydrogel male mold;
(4) macromolecule prepolymer and curing agent are mixed to get mold solution.Mold solution can be the methyl methacrylate pre-gathering solutions that contains light trigger, contain the dimethyl silicone polymer oligomer of curing agent and contain epoxy resin of curing agent etc.; With mold solution, water on hydrogel male mold, cover that cover plate makes and itself and hydrogel male mold between the gap be full of mold solution, treat that mold solution curing and demolding can have the micro-fluidic chip substrate of microchannel structure, after encapsulating with the micro-fluidic chip cover plate, get the polymeric micro-fluidic chip finished product.
Among the present invention, photoresist layer described in the step (1) is that thickness is the 10-60 micron, be that (position that the microchannel structure is namely arranged is black to positive if be designed with the mask of micro-fluidic chip microchannel structure, other partially transparents, such as accompanying drawing 1), need select negative photoresist, such as the SU-8 photoresist.If mask is negative film, then need select positive photoresist, what get by optical graving like this is the photoresist former.
Among the present invention, (namely being heated to uniform temperature can melt the thermal reversibility that needs the consideration hydrogel of selecting of the macromolecular material of the hydrogel of preparation described in the step (2), be cooled to uniform temperature gelling can occur) so that the melting of hydrogel male mold copies and reclaims.The present invention has selected agar and these two kinds common macromolecular material preparation hydrogels of gelatin, and the crosslinking agent of agar hydrogel and gelatin hydrogel is selected respectively borax and alum, and consumption all must not surpass 1%, otherwise Precipitation is arranged.In addition, also need add a certain amount of glycerine as plasticizer, to improve toughness and the moisture retention of hydrogel.The prescription of agar hydrogel is: agar 5-15%, glycerine 1-8%, borax 0.1-1%, water surplus; The prescription of gelatin hydrogel is: gelatin: 15-40%, glycerine 5-30%, alum 0.1-1%, water surplus.In addition, starch also can be used for the making of elastic hot reversible hydrogel.
Hydrogel male mold among the present invention, in the step (3) agar hydrogel or the gelatin hydrogel of melting watered after the photoresist female mold surfaces, needs hair side with frosted glass cover on the hydrogel of melting and depress, so that can firmly be attached on the sheet glass.The gap of photoresist former and frosted glass plate is 0.5-1.0mm and the hydrogel that is full of melting.In addition, the bath temperature of fusing agar hydrogel and gelatin hydrogel is controlled at respectively 60-80 and 70-95 ℃, and the cooling forming temperature that is sandwiched in the melting hydrogel between photoresist former and frosted glass plate is controlled at respectively 10-30 ℃ and 5-25 ℃ to agar hydrogel and gelatin hydrogel.The cooled and solidified time is 5-15 minute.
Among the present invention, used macromolecule prepolymer mixes the mold solution that makes in the step (4) with curing agent needs to solidify at room temperature condition, and requires the curing reaction heat release seldom.The epoxy resin that the mold solution that the present invention uses has the methyl methacrylate pre-polymer solution that contains light trigger, the dimethyl silicone polymer oligomer that contains curing agent and contains curing agent etc. all can be in cold curing.
Among the present invention, the cover plate materials of step (4) middle cover on macromolecule prepolymer mold solution is identical with pre-prepared polymeric micro-fluidic chip, be mainly polymethyl methacrylate, dimethyl silicone polymer and epoxy resin etc., make by oneself by casting method with corresponding mold solution.This cover plate becomes the part of polymeric micro-fluidic chip behind solidified forming.During cast polymerization thing micro-fluidic chip substrate, the gap between cover plate and hydrogel male mold is 0.25-1.0mm and is full of mold solution.
The method for preparing polymeric micro-fluidic chip based on hydrogel male mold that the present invention proposes is described in further detail as follows:
Adopt the microchannel structure of computer aided design software Adobe Illustrator CS3 design micro-fluidic chip, typical design as shown in Figure 1, consisted of by single right-angled intersection microchannel and solution connection holes, adopt high-resolution (such as 3600dpi) laser photocomposing system to be printed as mask at transparent membrane, microchannel width on the mask is 20-100 μ m, solution connection holes diameter 1-2mm, wherein separate microchannel 2, sample intake passage 7 and solution hole 1,4,5 and 6 (accompanying drawing 1) and be black, remainder is transparent.Apply one deck negative photoresist 9 (such as SU-8 photoresists) at silicon chip 10 by the spin-coating technology, thickness is the 10-60 micron, then cover mask (containing the microchannel structure), after wavelength 365nm ultraviolet exposure and baking processing, with supporting developer immersion treatment, the flush away photoresist layer of section's exposed portion (microchannel structure) not in acetone and isopropyl alcohol respectively, then get photoresist former 11 after the photoresist sclerosis that baking partly exposes microchannel and solution connection holes in baking oven, the degree of depth of microchannel is 10-60 μ m.
The present invention adopts agar and two kinds of macromolecular materials of gelatin respectively for the preparation of the hot reversible hydrogel mould of polymeric micro-fluidic chip casting method processing, and the prescription of two kinds of hydrogels of use obtains after optimizing through great many of experiments.The prescription of agar hydrogel is: agar 5-15%, glycerine 1-8%, borax 0.1-1%, water surplus; The prescription of gelatin hydrogel is: gelatin: 15-40%, glycerine 5-30%, alum 0.1-1%, water surplus.In addition, starch also can be used for the making of elastic hot reversible hydrogel.The crosslinking agent of agar hydrogel and gelatin hydrogel is selected respectively borax and alum, and consumption all must not surpass 1%, otherwise Precipitation is arranged.In addition, also need add a certain amount of glycerine in the hydrogel as plasticizer, to improve toughness and the moisture retention of gel.According to above-mentioned prescription, in the water that first crosslinking agent and the plasticizer of formula ratio is dissolved in formula ratio clear solution, then add the corresponding macromolecular material such as agar or the gelatin that take by weighing by formula ratio.Can directly be heated to boiling and continuous the stirring until agar dissolves fully for agar, cool to room temperature can get the reversible moulage of agar hydrogel heat.For gelatin, need be dispersed in first in the aqueous solution that contains glycerine and alum, in 10-40 ℃ of swelling 3-12 hour, the then thoroughly dissolving in 60-90 ℃ of heating water bath 2-6 hour.Cool to room temperature gets agar hydrogel and gelatin hydrogel, all can be used as hot reversible moulage.
Before the preparation hydrogel male mold, the water-bath that first agar hydrogel and gelatin hydrogel moulage is placed temperature to be respectively 60-80 and 70-95 ℃ is melted.The hydrogel 8 of melting (is seen accompanying drawing 2) thereon along the center line casting on the long limit of photoresist former 11, then hydrogel male mold 13 covers the hair side of the frosted glass plate 12 of a slice preheating on the hydrogel 8 of melting and depresses, so that can firmly be attached on the sheet glass 12 after the cooled and solidified.Notice that needing the gap by pad adjusting photoresist former 12 and frosted glass plate 12 is 0.5-1.0mm, and the hydrogel 8 that requires this gap to be melted fills up, then be sandwiched in respectively cooling forming in 10-30 and 5-25 ℃ of temperature range of the agar hydrogel of 12 of photoresist former 11 and frosted glass plates and gelatin hydrogel, after 5-15 minute, the hydrogel male mold layer of cooled and solidified separates with photoresist former 11 together with frosted glass plate, gets hydrogel male mold 13.
Macromolecule pre-gathering solutions and curing agent are mixed to get mold solution 14, because use is hydrogel male mold, fusing point is lower, and the mold solution of selecting needs to solidify at room temperature condition, and requires the curing reaction heat release seldom.The epoxy resin that the mold solution commonly used that meets these conditions has the methyl methacrylate pre-polymer solution that contains light trigger, the dimethyl silicone polymer oligomer that contains curing agent and contains curing agent etc. all can be in cold curing.The methyl methacrylate solution that will be dissolved with light trigger benzoin ethyl ether (0.1-0.3% of methyl methacrylate quality) is the methyl methacrylate pre-polymer solution that irradiation can obtain to contain light trigger in 30-120 minute under the ultraviolet ray of 365nm in wavelength at room temperature condition; And the dimethyl silicone polymer oligomer mold solution that contains curing agent is that commodity dimethyl silicone polymer oligomer (such as 107 room temperature vulcanized silicone rubbers) is mixed acquisition with curing agent tetraethoxysilance and promoter dibutyl tin laurate, and wherein the content of tetraethoxysilance and dibutyl tin laurate is respectively 5% and 1-2%; The epoxy resin pattern solution that contains curing agent adopts commodity bisphenol A epoxide resins (such as E51 epoxy resin) and curing agent ethylene diamine to be mixed with, and wherein the content of ethylenediamine is 8-12%.Mold solution 14 is selected in the requirement for preparing as required chip, waters on hydrogel male mold 13, and covers cover plate 15 with pre-prepared polymeric micro-fluidic chip same material.Cover plate 15 is controlled in the 0.25-1.0mm scope by pad with the gap of hydrogel male mold 13, and requires this gap to be full of mold solution 14, becomes the part of polymeric micro-fluidic chip substrate 16 when mold solution 14 solidified formings and demoulding back shroud 15.Then, in the end punching ( solution connection holes 1,4,5 and 6 is seen accompanying drawing 1, aperture 1-2mm) of the microchannel of microchannel substrate 16.Because hydrogel male mold 13 is the hydrophilicity high elasticity body, the polymeric micro-fluidic chip substrate 16 of shaping has hydrophobic surface, therefore the demoulding is very easy.For the methyl methacrylate pre-polymer solution that contains light trigger that casts in 15 of hydrogel male mold 13 and cover plates, at room temperature 30 minutes polymethyl methacrylate micro flow control chip substrates that can harden fully to get of irradiation under the ultraviolet ray of 365nm get micro-fluidic chip finished product 18 through the cover plate 17 with same material after 108 ℃ of packaging by hot pressing.And for dimethyl silicone polymer oligomer and epoxy resin, in case add curing agent, its curing reaction begins immediately, therefore curing agent must add before the casting chip.Needed at ambient temperature 1-3 hour can be cured as elastomer for the dimethyl silicone polymer mold solution that casts in 15 of hydrogel male mold 13 and cover plates, the demoulding gets the dimethyl silicone polymer micro flow control chip substrate, it is irradiation after 20-60 minute under the ultraviolet ray of 365nm in wavelength, the unidimensional dimethyl silicone polymer cover plate of the one side that passage arranged and a slice is aimed at, and at room temperature pressurization encapsulation can get micro-fluidic chip finished product 18.Needed at ambient temperature 2-4 hour can be cured as rigid body for the epoxy resin pattern solution that casts in 15 of hydrogel male mold 13 and cover plates, the demoulding gets epoxy resin micro-fluidic chip substrate, and the substrate 16 that makes can get micro-fluidic chip 18 by packaging by hot pressing with the unidimensional epoxy resin cover plate 17 that a slice scribbles absolute ethyl alcohol in 100-150 ℃ of temperature range.
The present invention has prepared the polymeric micro-fluidic chip processing reversible hydrogel male mold of elastic hot, and is used for the processing of micro-fluidic chip.Owing to being elastic mould, the demoulding is very easy, and can repeatedly use.This novel formpiston can directly water the hydrogel that melts at the photoresist former and carry out batch duplicating, the every reproducible thousands of hydrogel male molds of photoresist former, have lower cost for material, easy, the melting of being shaped reclaims and biodegradable advantage, in the low-cost processing of the batch of polymeric micro-fluidic chip good application prospect arranged.
Description of drawings
Fig. 1 is typical single right-angled intersection micro-fluidic chip design drawing of processing among the present invention.
Fig. 2 is that the fusion-cast method copies the flow chart that hydrogel male mold (A-D) and hydrogel male mold surface casting method prepares polymeric micro-fluidic chip (E-I) among the present invention,
Wherein, (A) water melting hydrogel 8 on photoresist former 11 and depress; (B) lid frosted glass plate 12; (C) cooled and solidified; (D) hydrogel male mold 13 separates with photoresist former 11; (E) will be watered by the mold solution 14 that macromolecule prepolymer solution and curing agent form on hydrogel male mold 13; (F) will cover on mold solution 14 with the thin plate 15 of pre-prepared polymeric micro-fluidic chip same material and depress; (G) mold solution 14 solidified formings; (H) demoulding; (I) substrate 16 gets polymeric micro-fluidic chip finished product 18 (end view) with cover plate 17 bondings.
Fig. 3 is the microphotograph of the microphotograph of microchannel mould section outstanding on (a) gelatin hydrogel formpiston and the polymethyl methacrylate micro flow control chip substrate sample introduction right-angled intersection passage that (b) copies with the gelatin hydrogel formpiston.
Fig. 4 is for using among the present invention the electron scanning micrograph in polymethyl methacrylate micro flow control chip with the processing of gelatin hydrogel formpiston (a) and rear (b) microchannel cross section of encapsulation before encapsulation.
Fig. 5 is the electrophoresis pattern of polymethyl methacrylate micro flow control chip separating Li (a), potassium (b) and the sodium ion of the preparation of use the technology of the present invention.
Number in the figure: 1 is the sample solution hole, 2 for separating microchannel, 3 for containing microchannel 2 and 7 and solution connection holes 1,4,5 and 6 micro-fluidic chip, 4,5 and 6 are the cushioning liquid hole, 7 is the sample introduction microchannel, 8 are the melting hydrogel, and 9 for being processed with the photoresist layer of microchannel, and 10 is silicon chip, 11 is the photoresist former, 12 is frosted glass plate, and 13 is hydrogel male mold, and 14 is the mold solution that is comprised of macromolecule prepolymer solution and curing agent, 15 is the thin plate with pre-prepared polymer chip same material, 16 is the polymeric micro-fluidic chip substrate, and 17 are and the cover plate of pre-prepared polymer chip same material, and 18 is polymeric micro-fluidic chip finished product (end view).
The specific embodiment
Further describe the present invention below by embodiment and accompanying drawing:
Embodiment 1, the application of gelatin hydrogel formpiston in the polymethyl methacrylate micro flow control chip preparation
(1) design of micro-fluidic chip
Adopt microchannel and the solution connection holes of Adobe Illustrator CS3 Software for Design chip, adopt high-resolution (3600dpi) laser photocomposing system to be printed as the mask positive at the polyester transparent film, microchannel width on the mask is 50 μ m, solution connection holes is the circular hole of diameter 2mm, wherein microchannel (split tunnel 2 and sample intake passage 7) and solution hole 1,4,5 and 6 (accompanying drawing 1) are black, and remainder is transparent.Accompanying drawing 1 is seen in the modular design of micro-fluidic chip.Separate microchannel 2 long 65mm, sample introduction microchannel 5 long 10mm, wherein microchannel 4 and 5 crosspoints are 5mm to the distance of three nearest solution connection holes.This micro-fluidic chip design length is 75mm, designs the wide degree 16mm that is.
(2) making of SU-8 photoresist former
Be that 4 inches silicon chip 10 surface is by spin-coating technology (rotating speed 2500rpm at diameter, 50 seconds) (model is SU-8 to apply one deck negative photoresist 9, U.S. MicroChem company), 40 minutes (exposure front baking) of baking in 65 ℃ of baking ovens, then cover mask (the microchannel structure that contains design), compress with quartz glass plate (2mm is thick), 30min (365nm exposes under ultraviolet ray, 45W), baking 25 minutes (baking after the exposure) in 65 ℃ of baking ovens, with the supporting developer immersion treatment of SU-8 after 90 seconds, respectively in acetone and isopropyl alcohol rinsing 20 seconds with the flush away photoresist of section's exposed portion (microchannel and solution connection holes region) not, then baking made the photoresist sclerosis that microchannel and solution connection holes partly expose on the silicon chip 10 in 10 minutes in 150 ℃ of baking ovens, got SU-8 photoresist former 11.
(3) making of gelatin hydrogel formpiston
After 12 gram water and 6 are restrained glycerine and mix, add 0.2 gram alum, stirring has made dissolving, then 10 gram gelatin are dispersed in this solution, swelling is 6 hours under room temperature (approximately 25 ℃), then in the thoroughly dissolving in 3 hours of 75 ℃ of heating water baths, cool to room temperature gets elasticity gelatin hydrogel moulage.
Before the preparation gelatin hydrogel formpiston 13, first the gelatin hydrogel moulage is placed the water-bath of 80 ℃ of temperature to melt.After the hydrogel 8 of getting 1.5 milliliters of meltings casts on the former along the center line on the long limit of photoresist 11 formers, (hair side of 76.2mm * 25.4mm * 1.2mm) covers on the hydrogel 8 of melting and depresses, so that the hydrogel male mold 13 of cooling after coagulation can firmly be attached on the sheet glass 12 with the frosted glass plate 12 of a slice preheating.Notice that the gap that needs to regulate photoresist former 11 and frosted glass plate 12 by pad is about 0.7mm, and the hydrogel that requires to be melted by this gap fills up.The molten gelatin hydrogel 8 that is sandwiched in 12 of photoresist former 11 and frosted glass plates is at 10 minutes after coagulations of 10 ℃ of coolings, and 13 layers of the hydrogel male molds of shaping separate with photoresist former 11 together with frosted glass plate 12, get gelatin hydrogel formpiston 13.The microphotograph of outstanding microchannel mould section is seen accompanying drawing 3 (a) on the gelatin hydrogel formpiston.
(4) preparation of polymethyl methacrylate micro flow control chip
The methyl methacrylate solution that will be dissolved with light trigger benzoin ethyl ether (methyl methacrylate quality 0.2%) is the methyl methacrylate pre-polymer solution that irradiation can obtain to contain light trigger in 60 minutes under the ultraviolet ray of 365nm in wavelength at room temperature condition.Get 1.5 milliliters of these mold solution 14 and water thereon along the center line on the long limits of gelatin hydrogel formpiston 13, and cover a slice polymethyl methacrylate cover plate 15 (75mm * 16mm * 1.0mm).Cover plate 15 is controlled to be 0.5mm with the gap of hydrogel male mold 13 by pad, and requires this gap to be full of mold solution 14.At room temperature, the ultraviolet ray irradiation mold solution with wavelength 365nm can harden 15 parts that become micro-fluidic chip substrate 16 of polymethyl methacrylate cover plate in 30 minutes fully.After the demoulding in the terminal borings of substrate 16 microchannels ( solution connection holes 1,4,5 and 6 is seen accompanying drawing 1, aperture 2mm).Because hydrogel male mold 13 is the hydrophilicity high elasticity body, polymethyl methacrylate micro flow control chip substrate 16 surfaces of shaping are hydrophobicity, therefore the demoulding is very easy.Be coated in above-mentioned pre-gathering solutions on a slice sheet glass and be pressed on another sheet glass, distance between two glass plates can be controlled by the transparent dacron membrane that sticks 80 microns of thickness in the inboard, four limits of glass plate, with getting polymethyl methacrylate cover plate 17 after UV-irradiation initiation polymerisation in bulk and the demoulding, be the small pieces that are of a size of 75mm * 16mm with front reduction.Micro-fluidic chip substrate 16 and the flushing of cover plate 17 waters with channel end boring, after drying up, apply oxolane one time at cover plate, immediately substrate 16 and cover plate 17 are closed, apply the pressure of 2 kg/cm by two smooth glass plywoods, in 106-107 ℃ of baking oven, keep 10min, take out and naturally cool to room temperature, namely finish the encapsulation of substrate 16 and cover plate 17, get polymethyl methacrylate micro flow control chip finished product 18.
The microphotograph of the polymethyl methacrylate micro flow control chip substrate sample introduction right-angled intersection passage that copies with gelatin hydrogel formpiston 13 is seen accompanying drawing 3 (b).Use the electron scanning micrograph in polymethyl methacrylate micro flow control chip microchannel cross section before and after encapsulation of gelatin hydrogel formpiston processing among the present invention to see accompanying drawing 4.Wherein the height of the microchannel of processing is 33.2 μ m, width is 48.8 μ m, and the result shows the microchannel structure that adopts the technology of the present invention successfully to process and copied design, and fidelity is higher, the polymethyl methacrylate micro flow control chip channel design of preparation is complete, and quality is satisfactory.
(5) application of the polymethyl methacrylate micro flow control chip of preparation
The polymethyl methacrylate micro flow control chip that the present invention makes and 0-3000V high-voltage DC power supply and electricity are led detector formation micro-fluidic chip electricity and are led detection system, successfully be used for lithium ion, three kinds of cationic electrophoretic separation of sodium ion and potassium ion, the 0.1mM lithium ion (a) that records, 0.1mM the electrophoresis pattern of sodium ion (b) and 0.1mM potassium ion (c) is seen accompanying drawing 5, test condition is: separation and sample introduction voltage are+1000V, sample injection time is 2s, cushioning liquid is 20mM boric acid-20mM trishydroxymethylaminomethane mixed solution (pH 8.0), electricity is led detection waveform and is sinusoidal wave (frequency is 400kHz, and the P-to-P voltage amplitude is 5V).The result shows, the polymethyl methacrylate micro flow control chip that the present invention makes can will separate above-mentioned three kinds of cations in 100 seconds fully, and is fast efficient, and good application prospect is arranged in the actual sample analysis.
(1) making of agar hydrogel male mold
The making of the design of micro-fluidic chip and SU-8 photoresist former 11 is with embodiment 1.
After 81.5 gram water and 5 are restrained glycerine (plasticizer) and mix, add 0.5 gram borax stirring and make its dissolving, then 13 agar are dispersed in this solution, are heated to boiling and continuous stirring until play fully dissolving, cool to room temperature gets elasticity gelatin hydrogel moulage.
Before the preparation agar hydrogel male mold, place the water-bath of temperature 70 C to melt agar hydrogel stamps material first.The hydrogel 8 of getting 1.5 milliliters of meltings along the center line casting on photoresist former 11 long limits thereon, then (hair side of 76.2mm * 25.4mm * 1.2mm) covers on the hydrogel 8 of melting and depresses with the frosted glass plate 12 of a slice preheating.Notice that the gap that needs to regulate photoresist former 11 and frosted glass plate 12 by pad is about 0.7mm, and the agar hydrogel 8 that requires this gap to be melted fills up, then in 25 ℃ of coolings postforming in 10 minutes, the hydrogel male mold layer of cooled and solidified separates with the photoresist former together with frosted glass plate, gets agar hydrogel male mold 13.
(2) preparation of dimethyl silicone polymer micro flow control chip
Commodity dimethyl silicone polymer oligomer 107 room temperature vulcanized silicone rubbers are mixed with curing agent tetraethoxysilance and promoter dibutyl tin laurate, must contain the dimethyl silicone polymer oligomer mold solution of curing agent, wherein the content of tetraethoxysilance and dibutyl tin laurate is respectively 5% and 1.5%; Get 1.5 milliliters of these mold solution 14 and water thereon along the center line on the long limits of agar hydrogel male mold 13, and cover the transparent dimethyl silicone polymer cover plate 15 of a slice (75mm * 16mm * 1.0mm).Cover plate 15 is 0.5mm and is full of mold solution 14 with the gap of hydrogel male mold 13, at room temperature, can solidify fully after 2 hours.Dimethyl silicone polymer cover plate 15 becomes the part of polymeric micro-fluidic chip substrate 16 behind mold solution solidified forming, after the demoulding in the terminal punchings of substrate 16 microchannels ( solution connection holes 1,4,5 and 6 is seen accompanying drawing 1, aperture 2mm).Before the encapsulation, micro-fluidic chip substrate 16 and a slice are reduced the micro-fluidic chip cover plate 17 (75mm * 16mm * 1.0mm) clean with absolute ethyl alcohol that forms with transparent dimethyl silicone polymer thin plate, dry up, it is irradiation after 30 minutes under the ultraviolet ray of 365nm in wavelength, substrate 16 has a cover of passage on micro-fluidic chip cover plate 17, and at room temperature pressurization encapsulation can get dimethyl silicone polymer micro flow control chip finished product 18.
(3) preparation of epoxy resin micro-fluidic chip
With commodity E51 epoxy resin mix with curing agent ethylene diamine and vacuum outgas after, the epoxy resin pattern solution that can contain curing agent, get 1.5 milliliters of these mold solution 14 and water thereon along the center line on the long limits of agar hydrogel male mold 13, and cover a slice self-control transparent epoxy resin cover plate 15 (75mm * 16mm * 1.0mm).Cover plate 15 is 0.5mm and is full of mold solution 8 with the gap of hydrogel male mold 13.At room temperature, can harden fully in 3 hours.Epoxy resin cover plate 15 becomes the part of polymeric micro-fluidic chip substrate 16 behind mold solution 8 solidified formings, the terminal boring of microchannel ( solution connection holes 1,4,5 and 6 is seen accompanying drawing 1, aperture 2mm) on substrate 16 after the demoulding.Before the encapsulation, with micro-fluidic chip substrate 16 and a slice self-control epoxy resin cover plate 17 (75mm * 16mm * 1.0mm) clean and dry up with water-ethanol, apply absolute ethyl alcohol one time at cover plate 17, immediately substrate 16 and cover plate 17 are closed, apply the pressure of 3 (kg/cm) by two smooth glass plywoods, in 130 ℃ of baking ovens, keep 10min, take out and naturally cool to room temperature, namely finish the encapsulation of substrate 16 and cover plate 17, get epoxy resin micro-fluidic chip finished product 18.
Claims (4)
1. the method for preparing polymeric micro-fluidic chip based on hydrogel male mold is characterized in that comprising the steps:
The microchannel structure that (1) will design the micro-fluidic chip on mask by photoetching is transferred in the photoresist layer, gets the photoresist former;
(2) will be dissolved in the aqueous solution that contains crosslinking agent and plasticizer by heating for agar or the gelatin of preparation hydrogel, get hot reversible hydrogel stamps material after the cooling;
(3) with after agar or the reversible hydrogel stamps material heat fused of gelatin heat, water on the photoresist former, and the hair side of frosted glass plate covered on the hydrogel of fusing, after its cooled and solidified, it is separated with the photoresist former together with frosted glass plate, get hydrogel male mold, the gap of photoresist former and frosted glass plate is 0.5-1.0mm and is full of the melting hydrogel;
(4) macromolecule prepolymer and curing agent are mixed to get mold solution, mold solution is watered on hydrogel male mold, covering cover plate makes the gap between itself and hydrogel male mold be full of mold solution, treat that mold solution curing and demolding must have the micro-fluidic chip substrate of microchannel structure, after encapsulating with the micro-fluidic chip cover plate, get the polymeric micro-fluidic chip finished product;
Described mold solution is the methyl methacrylate pre-gathering solutions that contains light trigger, contain the dimethyl silicone polymer oligomer of curing agent or contain the epoxy resin of curing agent.
2. preparation method according to claim 1 is characterized in that each component of described agar hydrogel and percentage by weight thereof are: agar 5-15%, glycerine 1-8%, borax 0.1-1%, water surplus; Each component and the percentage by weight thereof of described gelatin hydrogel are: gelatin 15-40%, glycerine 5-30%, alum 0.1-1%, water surplus.
3. preparation method according to claim 1 is characterized in that in the step 3, and the temperature that is used for fusing agar hydrogel and gelatin hydrogel is respectively 60-80 ℃ and 70-95 ℃; Agar hydrogel and gelatin hydrogel cooling forming temperature are respectively 10-30 ℃ and 5-25 ℃; The cooled and solidified time is 5-15 minute.
4. method for preparing polymeric micro-fluidic chip according to claim 1, it is characterized in that in the step (4) with the mold solution that macromolecule pre-gathering solutions and curing agent are made into be sandwiched in hydrogel male mold and and the cover plate of pre-prepared polymeric micro-fluidic chip same material between, the gap of hydrogel male mold and cover plate is 0.25-1.0mm and is full of mold solution.
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| CN104130932B (en) * | 2014-07-30 | 2016-05-25 | 华中科技大学 | A kind of Enrichment of bacteria device based on agarose micro-fluidic chip |
| CN106349487B (en) * | 2016-08-17 | 2019-03-01 | 深圳市微纳集成电路与系统应用研究院 | A kind of preparation method of the hydrogel with microfluidic channel |
| CN108597335A (en) * | 2018-06-15 | 2018-09-28 | 安徽中医药高等专科学校 | A kind of preparation method of green multifunctional teaching microchip |
| CN109839367A (en) * | 2019-01-29 | 2019-06-04 | 天津大学 | Hydrogel shape coding and the decoded method of image procossing for food toxin detection |
| CN110041942B (en) * | 2019-04-24 | 2021-09-10 | 上海工程技术大学 | Microencapsulated soil conditioner and preparation method thereof |
| CN111007698B (en) * | 2019-11-26 | 2023-08-25 | 江苏汉拓光学材料有限公司 | Bio-based water-soluble negative ultraviolet photoresist composition, photoresist and preparation method thereof |
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