基于PDMS的經(jīng)濟(jì)型微流體加工技術(shù)研究*

張雅雅，崔建國(guó)重慶理工大學(xué)藥學(xué)與生物工程學(xué)院，重慶 400054

1．Introduction

Microfluidic technology can be controlled，operated and tested in microscopic dimensions，which is an emerging interdisciplinary based on microelectronics， micromechanical， bioengineering and micronano technology［1］．Last decade，the development of microfluidic technology was very rapidly，brought a dramatic change in the field of medicine，chemistry and life sciences，and some of the company was committed to industrialize microfluidic technology［2］．The equipment related to microsystem including micropump，microvalve，micromixer，microfilter，and micro splitter，etc［3］．Microfluidic chip is an implementation platform for microfluidic technology，and its essence is processed 10～100μm width channel systems by using micro-processing technology on the substrates，mainly based on analysis chemistry，biochemistry，and micro electromechanical processing technology．It’s the key point of micro total analysis systems in current development，since microfluidic chips play great application value in these areas［4-5］．In order to fabricate micro pipeline network structure in microfluidic chips，the processing technology plays a very important role．

For microfluidic chip processing technology based on PDMS，the more classical method is maskbased lithography，but the processing of mask requires higher cost，longer time-consuming，and more expensive lithography machines and special machinery，which are difficult to meet the needs of rapid processing．Therefore，this method cannot be carried out in an ordinary laboratory ［6］．In this paper，current novel and relatively fast processing PDMSmicrochannel structure method is reviewed，such as the economical laser erosion and projector lithography technology［7-8］．For the treatment of PDMSsurface wettability，the classical method is to use the more expensive plasma etching machine，after activating functional groups on PDMS surface，ideal modified result can be obtained．But the expensive cost of this method is not suitable for ordinary laboratory，the alternative method is to use microwave and vacuum ultraviolet surface modification technology［9］．Microfluidic chip multilayer structure alignment and the unreversible packaging has always been a difficulty．This paper discusses the self-aligned bonding and reversible plug bonding technology．Combination of both can better solve the above difficulty，which can realize self-aligned bonding of multilayer PDMSstructures and reversible packaging［10-11］．By comparing the existing microfluidic processing technology based on PDMS，this paper integrates a set of economic microfluidic processing technology．As a useful complement to traditional classical processing methods，these methods do not need expensive special equipment，and can be carried out in an ordinary laboratory．

2．The structure，performance and preparation of PDMS

Polydimethylsiloxane(PDMS)is a common high molecular polymer material，and it has advantages of low cost，simple processing，and also has low surface energy，excellent optical transparency，durability，insulating，as well as biocompatibility characteristics．Thus，this material is commonly used to process the microfluidic chip by soft lithography［12-13］．It’s a silicone(silicone rubber)material，and containing the structural units—(CH3)2SiO—．The polymer molecular structure is shown in Figure 1．

Figure 1．Structure of PDMS

In conventional microfluidic chips，the general method of making PDMSmaterials is:A weight ratio of 10:1 is fully mixed with polymer base and curing agent of PDMS(Sylgard 184，Dow Corning)，fully stirred 5 min，placed in a vacuum desiccator degassing 0．5 h，and PDMSprepolymer is then obtained;the prepolymer is poured into the exposed photoresist molding or other models for degassing 0．5 h，and then placed on a hot plate and heated at a temperature of 80℃ for 2 h，after cooling the cured PDMS chips are obtained［9］．If the prepolymer is pouring on a glass slide，setting the speed of the coating machine，spinning coating a certain time，PDMS substrates with different thickness are obtained．Table 1 is the results of our laboratory tests．

Table 1．Relationship of PDMS thickness and the spin speed of dumped plastic machine

3．Fabricating micro-structure of PDMS

3．1．Laser erosion templateless processing technology

The microchannel structure based on PDMSproduction process needs mask，but the mask process，such as lithography photoresist or silicon deep reactive ion etching，etc．，all need to spend longer time and higher cost．Accordingly，in microfluidic and MEMS(microelectromechanical systems)，fast and straightforward PDMSmicrostructure machining technology is very important，therefore the laser erosion technique can rapidly process the microfluidic chip．

By summing up the traditional laser engraving shortcomings when fabricating PDMSmicrostructures，Hao-Bing Liu and others put forward the use of CO2laser，through cutting and pattern transfer(TC＆T)process to fabricate PDMSmicrostructures，and finally obtain better results［7，14］．TC＆T process for templateless fabrication of PDMS microstructures is shown in Figure 2．

Figure 2．Process for templateless fabrication of PDMS［7］

In this way，a smooth channel bottom is obtained，due to removing the mask and precision machining process equipment consumables，thus can greatly reduce the time and cost of the molding．Through TC＆ T process，the feature structures with depth range of 2 μm ～3．6 mm and the aspect ratio of 10:1 can be obtained，wherein the minimum lateral feature size can reach 30μm(limited by the scanning accuracy and laser spot size)．The lateral resolution of this technology is not higher than the photolithography mask，but compared to the complex process of production of the mask，it is more suitable for microfluidic applications．If the application field of the lateral feature size is not very critical，this fast and low cost method can be widely used to process PDMS microstructures．Such as CO2laser can be used to quickly processed microfluidic devices on PDMS［15］．

3．2．Projector lithography(DP2)method

In recent years，in field of microfluidic precision processing technology，in order to overcome the flaws and shortcomings of inflexibility，complexity and high cost of operating，many scholars have carried out alternative researches，wherein the consumer electronics products with high precision to simplify precision machining have achieved good results，this inexpensive tool can rapid replicate microscopic model［16-18］．First，the laser printer is used to make transparent mask(replaced the traditional chromiumbased mask)，then the micropattern can be directly obtained via the projector projection and exposure on the light-sensitive membrane［17］．Such technology can achieve accuracy about 100μm，it can reduce the time and cost of the rapid prototyping process．

In order to overcome the shortcomings of precision processing technology，especially high costs，and can be carried out the templateless process out of clean-room，Si-wei Zhao，et al．，proposed a method that referred to the directed projection on dry-film photoresist(DP2)，by means of processing a printed-circuit-board on photosensitive film．Such direct method using non-contact mask design，exposing the photosensitive polymer to form a structure，and the dry-film resist process is simplified，and can be used for precision machining of the photosensitive polymers and microfluidic structures［8］．In an ordinary laboratory，this method can produce a complex three-dimensional microfluidic structure within one hour．More importantly，compared to all the maskless lithography technology，DP2 is relatively simple to set，only needing a digital projector and an adjustable optical lens，can achieve high accuracy(10 μm)and high alignment accuracy(＜10μm)．In addition，it is an environmentally friendly and non-toxic process．The working principle is shown in Figure 3．

Figure 3．Illustration of the DP2 process［19］

Due to the projector device and the chip itself limited，the exposure area obtained by this method is relatively limited．But generally speaking，compared with DP2 and other precision machining technology out of cleanroom，DP2 is simple，does not require a photomask or UV light source，and has high resolution(10 μm)，which is suitable for rapid micro model processing in general laboratory［16，19］．

4．Wettability on the modified PDMS surface

In the field of biomedical，as implant materials and medicines carrier，PDMS can enter the body．But the hydrophobic surface may cause adverse reactions of the human body，and the modification treatment need to be done［20］．Meanwhile，in the field of microfluidic，PDMSmaterials are often used as micro-reactor substrates，they are also required to be modified on their flexible surface，and oxygen plasma is the more commonly used method of modifying the surface of materials［21］．PDMS is a hydrophobic polymer，after exposure oxygen plasma，along with oxidation，chain scission and cross joint，silicon surface is formed，so it becomes hydrophilic structure［22］．Furthermore，the oxygen plasma treatment may also be used to permanently bonding between the polymer and the silicon-based material［23］．

Although this technology has many advantages，the oxygen plasma surface treatment requires special equipment(such as plasma machine)，and its expensive price and other factors do not applicable to most ordinary laboratory．

4．1．PDMSsurface modification using vacuum ultraviolet

Yao Shuyin，et al．，proposed that using vacuum UV light can significantly delay the recovery time of PDMS hydrophobicity，and improve the biocompatibility［24］．Specific operations are as follows，using a vacuum ultraviolet light irradiation device UER20-172 V，the sample is sealed in a chamber with a vacuum pressure of about 500 Pa，and then it is irradiated for several minutes．After irradiation，the hydroxyl groups is formed on material surface，which greatly increased the hydrophilicity on the surface of the PDMS．By measuring the contact angle，irradiating 10 min can almost reach 0°，place a short time later，the contact angle is gradually increased to 73°．Compared with other modification methods，this method can obtain better experimental results．If the modified PDMS samples immediately put into the water，two months later the measurement of contact angle is still close to 0°，which proves that water environment can prevent PDMS chain flip，help keep the surface hydrophilic，thereby facilitating to maintain the surface hydrophilic．

4．2．Microwave modification on the surface of PDMS

Brent T．Ginn and Oliver Steinbock designed and tested an economical method to replace conventional commercial oxygen plasma treatment equipment，i．e．，relying on an unmodified kitchen microwave oven(microwave discharge function)and standard laboratory glass desiccator［9］．Specific way of plasma treatment is:using ethanol rinse to clean prepared PDMS samples in advance，and to prevent accumulation of surface residues;after washing，sample is dried with compressed air，and placed on a glass slide;then the slide and some steel(function is generated spark and start oxygen decomposition while the microwave discharging)is placed in the vacuum desiccator;Oxygen is filled into the desiccator for two minutes，and then the pressure is degassed to 10-3Torr;Finally，the desiccator is placed in a microwave oven，microwave power is adjusted to the maximum，and performed 25 s plasma treatment．By testing the experiment of hydrophilicity on the surface of the PDMS(contact angle measurements)and plasma-induced adhesion force(bonding properties between PDMS and glass)，its reliability is confirmed．Using the microwave and conventional oxygen plasma cleaning machine to process PDMS surface，the changes of the contact angle are shown in Figure 4．

Figure 4．Contact angles between water and PDMSprocessed by microwave and oxygen plasma machine［9］

5．Bonding and packaging among PDMS chips

Packaging is one of the most challenging steps of micro-nanometer manufacturing，since most of the micro-devices contain more than one substrate．According to the assembly process，there are two most important factors:adhesion and alignment［25］．Traditional bonding techniques are usually used for silicon semiconductor manufacturing industry，and general processing environment requires high temperature(a few hundred to one thousand degrees)，heavy mechanical load， strong electric field， hermetically sealed device［26］，etc．In most of the microsystem applications，formed micropattern structure on polymeric material such as the wafer or PDMS，the above processes are harmful(especially for bioactive ingredients)．Therefore，it’s necessary for seeking constant reliable bonding packaging technology at low temperature．

5．1．Capillary adsorption self-assembly technique

Yu-zhe Ding，et al．put forward a kind of simple operation，package strategy—aapillary-driven Automatic Packaging(CAP)technology，successfully realize the self-assembly process［10］．Using this technology，the chip’s pattern can spontaneous adjustment and glue，and the two surfaces of the chip need to be treated by oxygen plasma and get hydrophilic．Specifically，the self-alignment and self-engagement of CAP process is using liquid capillary bridge，and three interfaces between the top and bottom substrates to achieve capillary interactions．Cap-illary interaction contains two physical forces:capillary force FCon the wetting borders and suction force FSfrom the negative Laplace pressure(ΔP)inside the liquid menisci［27］．As shown in Figure 5，the function of lateral component FC⊥of capillary force spontaneous aligns the both same comb-like surface structures by the surface energy of the liquid;the vertical component FC||of the suction capillary force can constantly evaporate followed with the capillary bridge，and gradually form intimate contact surface;gravity G of substrates may lead to some misalignments，and the substrates may not well perpendicular to the gravity plane．In order to maintain a negative adhesion to overcome the influence of gravity when moving，just the suspended bottom surface of the substrate is made underneath the fixed top surface，with the liquid evaporating，the bottom surface gradually closes to the fixed roof surface，and eventually packages together．Notably，F(xiàn)C⊥ is proportional to the number and the length of the comb-like structures，so when the bottom surface is not perfectly perpendicular to the gravity plane，the capillary force will be increased and drag the bottom surface to the alignment position;at the same time，the Laplace force of capillary bridge will move from the bottom surface to the top surface of the fixed，this force is larger than the gravity force．

Figure 5．Illustration of the principle of CAP［10］

CAP technology has high precision alignment(less than 10 μm)，better self-engagement and adhesion performance(larger than 300 kPa)．It can also realize multi-layer microstructures package，etc．In addition，this technique does not need any special equipment，does not involve heat treatment or mechanical treatment，so it’s very convenient to carry in general laboratory．Meanwhile，the self-alignment technique has been applied to the field of packaging microfluidics［28］．

5．2．Reversible pluggable package technology

Connection between macro and micro structure has always been the most complex and the worst reliability steps in microfluidic system development progress．Scholars have carried out a large irreversible(such as adhesive bonding)and reversible(pressfit)packaging technology research，trying to provide dedicated fluid channel between standard tubes and small piece of equipments，but none of these packaging technology is suitable for precision machining or difficult to miniaturization and integration［29-30］．Arnold Chen et al．，proposed a completely reversible，standard，and non-adhesive technology—Fit-to-Flow(F2F)．F2F adapter interconnect can make macro peripheral devices connect to the microfluidic chip［11］．It is similar to plug-and-play USB system in modern electronics，PDMS module with parallel tubes formed the socket．Therefore，a shape complementary component can simply insert，and constitute a mechanical seal of microchannel．

Specifically，Arnold Chen has carried out two distinct physical sealing mechanisms researches．One of which is to take advantage of the elastomeric sleeve tensile force to form a reversible seal，the other one is to use the negative pressure of vacuum pump to form the reversible interface seal(both are suitable for ordinary laboratory)．As shown in Figure 6，F(xiàn)igure 6(a)is reversible sealed with tension，simple structure，easy to plug，but less affordable leak pressure(about 60 kPa);Figure 6(b)is using vacuum negative pressure to form reversible seal，slightly complex structure，and external negative pressure source．The leakage pressure that can afford is related to the ratio between negative pressure and flow area．When the ratio is 4．7，it can reach to 336 kPa．F2F connection technology configures system for scalable multi-channel provides a common connection，at the same time F2F makes the microfluidic chip to be used repeatedly and pluggable，simple processing，especially suitable for ordinary laboratory．

6．Applications

Micropump is a very important part in microfluidic system，it can be effective for micro-liquid mixing，pumping，etc［5，31］．Using the above economical processing technology，it can be convenient to carry out processing microfluidic devices and systems in ordinary laboratory．Jian-guo Cui et al．，using the above methods，developed a simple structure of peristaltic micropump based on the principle of negative pressure driving［31］，as shown in Figure 7．Micropump consists of three layers PDMS materi-als，includes pneumatic layer，driving membrane layer and flow channel layer．The entire structures adopt the above methods to process，product and package．In particular，the pneumatic layer is connected with the negative pressure source，which can effectively remove the air bubbles in flow channel through PDMS driving membrane．This advantage is desired when dealing with complex fluid samples．The pump can be used in variety of biological and medical applications，such as point-diagnosis，cell culture，bodyfluid inspection，and drug development．

Figure 6．The general principles of F2F［11］

Figure 7．A vacuum-driven peristaltic micropump［31］

7．Conclusion

In this paper，the processing of microfluidic chips is analyzed，and different processing technologies are compared．Such as using volume control and spin coating to get the PDMSprepolymer，using CO2 laser cutting technology and DP2 technology to produce PDMSmicrochannel，using a vacuum UV irradiation and microwave oxygen plasma activation to modified PDMSsurface，and using CAP and F2F interface technologies which can form multilayer irreversible and reversible bonding between PDMS chips．These economic technologies do not need clean room and other specific environment，and are very suitable for ordinary laboratory．So they can completely become a useful supplement of traditional classical microfluidic processing technology．The reliability of these technologies have been confirmed，and have been applied to many microfluidic chip production and in application fields，such as in chemical，medicine and life sciences and other areas．

［1］ Whitesides G M．The Origins and Future of Microfluidics［J］．Nature，2006，442:368-373．

［2］ Yole Developpement company 4 years microfluidics technology to predict the future development trend［J］．Micronano-electronic Technology，2008，2:123-123．

［3］ Li yonggang．Studies on Key Processes and Techniques of PDMSMicrofludic Chips［D］．Graduate school of Chinese academy of sciences，2006．

［4］ Wang Ming．Study of Microfluidic Chip in Poly(dimethylsiloxane)［D］．Institute of Electronics Chinese Academy of Sciences，2003．

［5］ Farid Amirouche，Yu Zhou and Tom Johnson．Current micropμmp technology and their biomedical applications［J］．Microsystem Technology，2009，15(5):647-666．

［6］ JR Anderson，DT Chiu，RJ Jackman，et al．Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping［J］．Anal．Chem．，2000，72(14):3158-3164．

［7］ Liu H B， Gong H Q．Templateless prototyping of ploydimethylsiloxane microfludic structures using a pulsed CO2laser［J］．J．Micromech．Microeng，2009，19:1-8．

［8］ Zhao S，Cong H，Pan T．Direct projection on dry-film photoresist(DP2):do-it-yourself three-dimensional polymer microfluidics［J］．Lab Chip，2009，9:1128-1132．

［9］ Brent T．Ginn and Oliver Steinbock．Polymer Surface Modification Using Microwave-Oven-Generated Plasma［J］．Langmuir，2003，19(19):8117-8118．

［10］ Yuzhe Ding，Lingfei Hong，et al．Capillary-driven automatic packaging［J］．Lab Chip，2011(11):1464-1469．

［11］ Arnold Chen and Tingrui Pan．Fit-to-Flow(F2F)Interconnects:Universal Reversible Adhesive-Free Microfludic Adaptors Lab-on-a-Chip Systems［J］．Lab Chip，2011(11):727-732．

［12］ Jiang jiahuan．Biomedical microsystem technology and application［M］．Beijing:Chemical industry press，2006．

［13］ Jinwen Zhou，Amanda Vera Ellis，Nicolas Hans Voelcker．Recent developments in PDMSsurface modification for microfluidic devices［J］．ELECTROPHORESIS，2010(1):2-16．

［14］Snakenborg D，Klank H，Kutter JP．Microstructure fabrication with a CO2laser system［J］．J．Micromech．Microeng．，2004，14:182．

［15］ Huawei Li，Yiqiang Fan，et al．Fabrication of polystyrene microfluidic devices using a pulsed CO2laser system［J］．Microsystem Technology，2012，18:373-379．

［16］ Younan Xia and George．M．Whitesides．Microfabrication，Microstructures and Microsystems［J］．Angew．Chem．，1998，194:1-20．

［17］ Wei Wang，Siwei Zhao and Tingrui．Pan．Lab-on-a-print:from a single polymer film to three-dimensional integrated microfluidics［J］．Lab Chip，2009，9:1133-1137．

［18］ Limu Wang，Rimantas Kodzius，et al．Prototyping chips in minutes:Direct Laser Plotting(DLP)of functional microfluidic structures［J］．Sensors and Actuators B:Chemical，2012，168:214-222．

［19］ Focke M，Kosse D，Müller C，et al．Lab-on-a-Foil:microfluidics on thin and flexible films ［J］．Lab Chip，2010，10，1365-1386．

［20］ Efimenkoa K，Crowea J-A，Maniosh E，et al．Rapid formation of soft hydrophilic silicone elastomer surfaces［J］．Polymer，2005，46(22):9329-9341．

［21］ McDonald J C，Whitesides G M．Poly(dimethylsiloxane)as a Material for Fabricating Microfluidic DevicesAcc［J］．Acc．Chem．Res．，2002，35(7):491-499．

［22］ Hillborg H，Ankner JF．Crosslinked polydimethylsiloxane exposed to oxygen plasma studied by neutron reflectometry and other surface specific techniques［J］．Polymer，2000，41:6851-6863．

［23］ Cheng JY，Ross C A．Templated Self-Assembly of Block Copolymers:Top-Down Helps Bottom-Up［J］．Advanced Materials，2006，18(19):2505-2521．

［24］ YAO Shuyin，WU Zhongkui，YANG Jun．Research on hydrophilizition of polydimethysiloxane(PDMS)surface by vacuum ultraviolet radiation［J］．Journal of Hubei University，2010，32(2):188-199．

［25］ Kim JY，Baek JY．Photopolymerized check valve and its integration into a pneμmatic pμmping system for biocompatible sample delivery［J］．Lab Chip，2006(6):1091-1094．

［26］ Wei W，Pan T．From Cleanroom to Desktop:Emerging Micro-Nanofabrication Technology for Biomedical Applications［J］．Ann Biomed Eng，2011，39:600-620．

［27］ Gerlach A，Lambach H，Seidel D．Propagation of adhesives in joints during capillary adhesive bonding of microcomponents［J］．Microsyst Technol，1999(6):19-22．

［28］ Xing S，Zhao S，Pan T．Print-to-print:a facile multi-object micro-patterning technique［J］．Biomedical microdevices，2013:1-8．

［29］ Thorsen T，Maerkl S J，Quake S R．Microfluidic Large-Scale Integration［J］．Science，2002，298:580-584．

［30］ Arora A，Simone G．Latest Developments in Micro Total Analysis Systems［J］．Anal Chem，2010，82(12):4830-484．

［31］ Cui J G，Pan T．A vacuμm-driven peristaltic micropμmp with valed actuation chambers［J］．J．Micromech．Microeng，2011，21:1-7．