Nuclear Instruments and Methods in Physics Research B 306 (2013) 302–306

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Nuclear Instruments and Methods in Physics Research B

journal homepage: www.elsevier .com/locate /n imb

High speed microfluidic prototyping by programmable proximity aperture MeVion beam lithography

Nitipon Puttaraksa a,b, Mari Napari b, Leena Meriläinen a, Harry J. Whitlow b,1, Timo Sajavaara b,Leona Gilbert a,⇑a Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, Finlandb Department of Physics, University of Jyväskylä, Finland

a r t i c l e i n f o

Article history:Received 17 July 2012Received in revised form 12 December 2012Accepted 12 December 2012Available online 3 January 2013

Keywords:PPALPMMAMicrofluidicsIon beam lithography

0168-583X/$ - see front matter � 2013 Elsevier B.V.http://dx.doi.org/10.1016/j.nimb.2012.12.033

⇑ Corresponding author. Address: Department of BScience and NanoScience Center, P.O. Box 35, FI-40Finland. Tel.: +358 40 805 3859; fax: +358 14 617 23

E-mail address: leona.k.gilbert@jyu.fi (L. Gilbert).1 Present address: Institut des Microtechnologies Ap

Ingénierie, Eplatures-Grise 17, CH-2300 La Chaux-de-F

a b s t r a c t

Microfluidics refers to the science and technology for controlling and manipulating fluids that flow alongmicrochannels. For the development of complex prototypes, many microfluidic test structures arerequired first. Normally, these devices are fabricated via photolithography. This technique requires a pho-tomask for transferring a pattern to photoresists by exposing with UV light. However, this method can beslow when a new structure is required to change. This is because a series of photomasks are needed,which is time consuming and costly. Here, we present a programmable proximity aperture lithography(PPAL) technique for the development of microfluidic prototype in poly(methyl methacrylate) or PMMA.This method is based on using a mask made up of two movable L-shaped apertures in close proximity tothe target. The PPAL allows microfluidic chips that are designed with complex components having largeand small (�1 lm – �500 lm) pattern elements to be fabricated rapidly. In this paper, the fabricationprocess with test examples of microfluidic circuit designs is presented. Experimental results show thatnew patterns can be changed and produced in a few hours demonstrating that the PPAL technique is arapid method for development of microfluidic prototypes in PMMA.

� 2013 Elsevier B.V. All rights reserved.

1. Introduction

Microfluidics has been explored as a promising technology forresearch in small-scale sciences. By using these devices, there isa possibility to operate with a small volume of expensive samplesand reagents as well as to have a fast analysis. Moreover, thecomplex laboratory procedures e.g. sample preparation, mixer,analysis, etc. can also be integrated onto a single chip knownas a Lab-on-a-chip [1,2]. Due to these characteristic properties,microfluidic chips have been used in many applications such as cellsorters [3], PCR (polymerase chain reaction) [4] as well as high per-formance capillary electrophoresis (CE) [5].

A fast lithographic method is necessary for developing a com-plex microfluidic prototyping device. Integration of the compo-nents i.e. pumps, analysis chambers, valves as well as mixers ona single chip is an example of this case. Many chips are requiredfor testing the operating systems of the functions of the compo-

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iological and Environmental014 University of Jyväskylä,9.

pliquées Arc, Haute Ecole Arconds, Switzerland.

nents. Typically, microfluidic patterns are produced using conven-tional photolithography [6]. However, this method is not wellsuited when the pattern needs to be changed immediately or manytimes. This is because a new photomask is required for transferringthe new pattern on the sample. The photomask fabrication nor-mally requires 3–8 days [7]; therefore, it is important to have amethod where this step is eliminated.

Proton beam writing (PBW) [8] is one of the common types ofMeV ion beam lithography (MeV-IBL) that uses focused MeVprotons for creating micro and nanostructures. This methodhas been well-performed in making micro/nanofluidic devices[9] allowing a wide array of structures from rectangular to circu-lar, but speed of this technique is higher when writing smallerareas as compared to programmable proximity aperture lithogra-phy (PPAL) [10]. Recently, PPAL is another form of MeV-IBL thathas been developed and used for producing microchannels inboth positive [10,11] and negative [12] tones of poly(methylmethacrylate) or PMMA, as well as amorphous silica [13]. ThePPAL is a maskless method; therefore, the structures can easilybe changed. For this reason, the PPAL technique could initiallybe used for fabricating several microfluidic prototyping chips be-fore obtaining the final device. In this report, we demonstratethe fabrication of open and closed microfluidic devices and se-lected test circuits are presented.

Fig. 1. (a) A simulated pattern of an example microfluidic circuit. (b) Exposure of the pattern using the PPAL technique on PMMA coated Si wafer. (c) Microchannelsgeneration after development in a solution of 7:3 (IPA:DI water). (d) Closed microfluidic device fabricated by thermal bonding of a PMMA cap.

Fig. 2. An open microfluidic circuit composing of 500 lm � 500 lm inlet reservoirconnected with a capillary pump of 30 lm � 30 lm posts by a 100 lm widechannel. This device was fabricated using 3 MeV 4He2+ ions at the ion fluence of2.5 � 1013 ions cm�2.

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2. Experimental

Microfabrication in PMMA by PPAL has previously been re-ported as an effective way to perform lithography [10,11]. In thistechnique, a rectangular or square exposed area on the sample isadjustable and determined by two computer-controlled L-shapedaperture blades. In addition, a LABVIEW™ computer program con-trols the opening aperture area, the exposed sample position andthe beam on/off function. Generally, a rectangular or square writ-ing pattern element is defined by four coordinates (X1, X2, Y1 andY2), which are the upper left X, the lower X, the upper Y and thelower Y positions, respectively (see Fig. 1(a)). A complex structurecan be built up by connecting several pattern elements and thedetermination of all the coordinates of each pattern elements canbe calculated by means of a spreadsheet program, thus precisecontrol up to 100 nm increments of positions with 2 lm accuracyin bidirectional setting and 4 lm accuracy in position [10] allowsprevention of extensive stitching. Theoretically spherical struc-tures could be made with many rectangular patterns formulatinga circular pattern but in doing so stitching will occur. Prior to PPALexposure the layout is checked by visualization using a renderingprogram [14]. Fig. 1(a) illustrates a rendered image from a patternof 17 elements. The writing speed of the PPAL method with MeVions depends on three factors, which are the energy and speciesof the ions as well as the beam fluence. For an example in the caseof 3 MeV 4He2+ ions, the typical ion current is �0.07 nA measuredby the Faraday cup behind the L-shaped apertures of a200 lm � 200 lm opening area. The exposure time used with thision current is approximately 45 s per pattern element. This corre-sponds to an ion fluence of 2.5 � 1013 ions cm�2, which supportsour previous study [15]. The time for setting the new opening aper-ture size and moving the sample to the new position is about 30 s.Therefore, the total time for writing the pattern as shown inFig. 1(a) is approximately 22 min.

In order to investigate if the PPAL can be used to construct fastmicrofluidic prototyping in PMMA, closed-channel microfluidic de-signs were produced for characterizing fluid flow. At first, latentimage of the circuit was created on PMMA film spin coated on Siusing the PPAL technique as shown in Fig. 1(b). The samples usedin this study were prepared by spinning PMMA A11 of 950 kDa(Microchem™) at spin speed of 2500 rpm for 45 s on �1 cm� 1 cm silicon wafer. The excess PMMA solution was then removed

by soft-baking at 160 �C for 5 min. The processes were repeatedthree times to obtain �9 lm thick PMMA film. Subsequently, thesamples were developed in a solution of 7:3 (isopropyl alcohol:deionized, DI, water) by volume, followed by rinsing in DI water.Dissolving the exposed areas in a selective developer as seen inFig. 1(c) generated open microchannels. The closed microfluidicchannels were created by thermal bonding [16] in which a50 lm thick PMMA film (Goodfellow™) was used to cap the openchannels as depicted in Fig. 1(d). This was achieved by aligning thefilm under an optical microscope and heating on a hotplate at110 �C (above the glass transition temperature) for a few minutesunder action of a uniaxial force.

Capillary force was used in this experiment for actuating micro-fluidic circuits. Dyed deionized water (DI) was used as a workingfluid. The patterns and fluid flow were characterized by an opticalmicroscope (Brunel SP-400), which was connected to a Canon Pow-ershot A520 (10 fps for 640 � 480 pixels) camera. Typically, 5x and10x objective lens with combination of digital zoom from the cam-era were used for capturing images and videos.

Fig. 3. (a) Optical micrograph of a test microfluidic circuit produced in a 9 lm thickPMMA coated on Si using 3 MeV 4He2+ ions. (b) Closed-channels were sealed with50 lm thick PMMA film using thermal bonding. (c) Micrograph of red dyed DI waterfilling the closed microfluidic channels.

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3. Results and discussion

To demonstrate that PPAL system can be used for high speedmicrofluidic prototyping in PMMA, the following study was con-ducted. Fig. 2 illustrates an optical micrograph of a simplified cir-cuit of 9 lm PMMA/Si sample fabricated with 2.5 � 1013 ionscm�2 of 3 MeV 4He2+ ions. The structure consists of one fluid inletreservoir of 500 lm � 500 lm square area connected with the cap-illary pump of 30 lm � 30 lm posts via 100 lm wide channel.Experimental procedure revealed that this device was producedin 2 h. For this microfluidic device, the total time for fabrication

Fig. 4. (a) Optical micrograph of a closed zigzag microfluidic circuit of 20 lm wide chanthe microchannel at 0, 4 and 8 s, respectively.

of the micropillar capillary pump is longer than the summationtime of all producing steps as described by Mukhopadhyay et al.[17]. However, the PPAL is still considered to be a rapid method be-cause the entire circuit is directly written in PMMA in a single pro-cess step and hence the final capped circuit requires only twoprocess steps. Therefore, there is no need to make the time-con-suming stamp or master mold for transferring the structure toPMMA substrate. One of the problems of using the PPAL techniqueis the stitching area of each pattern elements where the fluencecan be doubled. This issue can be improved by writing the calibrat-ing patterns and using the second degree polynomial fitting curvebetween the opening aperture and the pattern sizes in X and Ydirections (data not shown). Based on this calibrating method,there was no stitching observed (see Fig. 2) as seen in other reports[12].

To examine a capillary driven fluid flow, a closed microfluidicdevice composing of several straight rectangular microchannelswas produced. Fig. 3(a) shows an optical micrograph of an open-channel microfluidic circuit fabricated by PPAL using the sameexperimental conditions as above in 9 lm thick PMMA film coatedon Si, after development in a solution of 7:3 (IPA:DI water) for5 min. The pattern consists of a 500 lm � 500 lm inlet reservoirconnected with the outlet reservoir of 500 lm � 500 lm areathrough the microchannels of 10, 20, 30, 50, and 80 lm widths cor-responding with the simulated pattern as shown in Fig. 1(a).Fig. 3(b) illustrates the closed microfluidic channels after bondingwith PMMA film of 50 lm thick using thermal bonding as previ-ously described (Section 2.2). Fabrication of this device took 1 h.The production of the PMMA chip in this experiment is also fasterthan a corresponding device in poly (dimethylsiloxane) or PDMS[18]. This is because many steps such as master mold fabrication,curing process for replicating structure from the mold, bondingmethod, drilling the holes for fluid inlet and outlet as well as mak-ing the fluidic connectors, are required in PDMS case. Furthermore,investigating the fluid flow in this PMMA chip was also rapid. Thiswas done by dropping a droplet of red dyed DI water into the inletreservoir without any using fluidic connectors. Fig. 3(c) reveals thered dyed DI water filling the microchannels by capillary force. This

nel fabricated by PPAL technique. Video frames in (b–d) of red dyed DI water filling

Fig. 5. Closed-channel microfluidic circuit where the channel width changed from 10 lm to (a) 30 lm and (b) 100 lm. Both chips were used for testing liquid meniscusstopping at the junction by changing channel geometry.

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flow has also been seen as reported by Feder et al. and Whitlowet al. [19,20]. The capillary forces are sufficient to be used for actu-ating fluid flow in microfluidics. These properties has already beenused for autonomous microfluidic system reported by Juncker et.al. [21]. In Fig. 3(c), the liquid meniscus stopped flowing at thejunction can be either a problem or useful. In the case of useful-ness, this can be acted as the passive capillary valve for controllingto close or open the fluid flow.

To further demonstrate that PPAL can be used for more com-plex microfluidic prototype, a zigzag microfluidic circuit designwith closed-channel as depicted in Fig. 4(a) was fabricated. In thisdevice, the open microchannel was engraved by the PPAL methodusing the same experimental conditions as above. The channeldepth of this device is �9 lm that corresponds to the thicknessof the PMMA resist film; whereas, the channel width is 20 lm.The aspect ratio of this channel structure, i.e. the ratio betweenthe height and the width of the channel, is approximately 0.5.This ratio is not considered to be high; however, the liquid canstill flow in this circuit compared to an open-channel becauseof the additional capillary force from the cap. The zigzag micro-fluidic circuit was produced in 1 h. Fig. 4 display images of timeseries of red dyed DI water flowing in the zigzag microfluidicchannel device. The result showed that there is no air trap inthe channel during the liquid meniscus filling the channel andthe structure was filled quite rapidly at a rate in agreement withMathur et al. [22].

To further investigate the PPAL capability for microfluidic appli-cation, the microfluidic circuits illustrated in Fig. 5(a) and (b) wereproduced. These structures were made using the same experimen-tal conditions as above in 9 lm thick PMMA coated on Si. Fabrica-tion of each chip was carried out in 40 min. Optical microscopydemonstrated that red dyed DI water menisci stopped flowing atthe junctions when the channel widths were changed from10 lm to 30 lm and 100 lm as depicted in Fig. 5(a) and (b),respectively. These devices were subsequently developed as a cap-illary passive valve.

Taken together, these experimental results indicate that thePPAL technique is flexible and an easy way to rapidly developnew microfluidic structures because the complete channel is pro-duced in a single lithography step and its direct writing nature.Generally, the new pattern can be made in few hours for a1 cm � 1 cm sample area. The writing speed of the PPAL methodfor microfluidic devices is longer than parallel exposure methodssuch as photolithography, but slightly shorter than the lithographyusing focused beams e.g. electron beam lithography, focused ion

beam lithography and proton beam writing [10]. In addition, thepattern writing in PPAL can be increased by using both higherion beam current and using faster linear positioners that can morerapidly position the apertures and sample. The results demonstratethat the PPAL system is suitable technique for fabricating a com-plex rectangular microfluidic prototype. However, there is a diffi-culty of using PPAL for producing nanostructures due to thelimited precision of linear positioners and the aperture edgeroughness.

4. Conclusions

In conclusion, the PPAL technique has been presented for fabri-cation of microfluidic devices in a few hours for a 1 cm � 1 cmsample. The new pattern can easily be changed by this approach.This has been shown to enable rapid development of microfluidicprototyping devices. Several circuits have been illustrated in thisreport that allowed fast capillary actuated flow in closed-channels.This could be further developed for a lab-on-a-chip (LOC) deviceused for fast and portable diagnostic tools [23].

Acknowledgements

This work was partially funded by European union (EU) grantagreement number 262411 and the Academy of Finland Center ofExcellence in Nuclear and Accelerator Based Physics, Ref. 213503and 251353. The funding sources had not involvement or role inthe development of this article.

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