On the Importance of Quality Control in Microfluidic Device

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Keywords: H-filter, laminates, laser ablation, quality control. 1. Introduction. The H-filter was designed for diffusion-based analyte extraction from one fluid stream.
ON THE IMPORTANCE OF QUALITY CONTROL IN MICROFLUIDIC DEVICE MANUFACTU~NG M.R. Steedman,

K.M. Lloyd, A. Hatch, MS. Munson, Univemity qf Washington, Seattle

P. Yager

Abstract The challenge of manufacturing microfluidic devices has been addressed with the development of various techniques such as micromachining, soft lithography, injection molding, and laser ablation [l]. Microfluidic devices constructed of laser-cut laminates (such as Mylar) are useful for rapidly prototyping new devices and for fabricating inexpensive and disposable microfluidic products [2]. However, a disadvantage of lasercut features is relatively poor feature resolution and the potential for generating rough edges. We demonstrate through both modeling and experiment that changes in performance can result from rough edges at a crucial junction of a microfluidic device. Keywords: H-filter, laminates, laser ablation, quality control 1. Introduction The H-filter was designed for diffusion-based analyte extraction from one fluid stream to an adjacent stream [3]. The device relies on analyte diffusion at the fluid-fluid The flat H-filter was designed to utilize a larger diffusion area than a interface. conventional H-filter [4]. In a study of laser-cut microfluidic devices containing the flat H-filter design, images of what was supposed to be a uniform ribbon of fluorescein solution appeared nonuniform (Figure 1). This spatially irregular but stable flow pattern was associated with anomalous mass transport across a supposedly flat interface between two apposed fluids. The effect was evident in regions free of upstream bubble formation. From this it was hypothesized that surface roughness at the flat H-filter splitting edge caused by irregular pullback (melting and contraction) of the Mylar during laser ablation modeling of the fluid flow was responsible for the anomalous flow. Three-dimensional and molecular diffusion were used to examine the effect of roughness at the splitting edge on the velocity and concentration fields. Modeling of defects at the splitting edge was based on profilometer measurements of laser-cut material. The model results predicted striping effects similar to those observed experimentally. 2. Theory The operation of the H-filter is dependent on stable laminar flow as experienced at low Reynolds numbers [5]. At the splitting edge in the flat H-filter device, areas of high pullback decrease the depth of the channel and create a higher fluidic resistance in these regions. Flow through the gaps between these pullback regions increases. As a result of this, in the regions upstream from a gap, a larger fraction of the channel depth will be occupied by the fluorescein solution. This is responsible for the characteristic “striped” pattern observed. The lack of turbulence allows the ridged interface downstream

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between the two apposed fluids to be stable and therefore persist along the length of the hannel (Figure 1).

Buffer

Pullback Z

t I,Y Figure 1. (Left) Unexpected distribution of analyte (fluorescein) in flat H-filter experiments. Images taken at different locations within the flat H-filter device. “Stripes” begin at the contact point of the two layers and are stable and reproducible. (Right) Schematic of entrance to the H-filter showing laser ablated pullback region on the splitting edge. 3. Experimental Flat H-filter devices were constructed of layers of Mylar cut using a 25W COZ laser as previously described [6]. A custom-built assembly jig was used to laminate the Mylar layers. The top inlet fluid (fluorescein in phosphate buffered saline, pH 7.4) was pumped at a constant flow rate of 750 nL/sec, and the bottom inlet fluid (buffer) was pumped at a constant flow rate of 450 nllsec. These flow rates corresponded to a low Reynolds number (0.05) in the main channel and were replicated in the computational simulations. We used a Tencor P15 Surface Profilometer (KLA-Tencor, Inc., San Jose, CA) to measure the edge roughness in the z-direction along the length (x-direction) of the splitting edge in an H-filter device similar to that used to generate the images in Figure 1. The resulting profile of the splitting edge is shown in Figure 2.

Figure 2. Roughness

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To model the splitting edge profile, the profilometer data was patterned after a castle battlement structure (Figure 3) by averaging the jagged peaks of the profilometer data into “crenels” (width, x-direction) and “merlons” (height, z-direction). Merlon heights ranged from 10 pm to 65 pm, and crenel widths ranged from 50 urn to 150 urn. Threedimensional models and flow simulations were conducted in Coventorware (Coventor, Inc., Gary, NC), a commercially available finite-element modeling package. A column integration plot was generated from the fluid simulations that modeled the mass fraction integration through the depth of the device to simulate what would be seen in a fluorescence micrograph (Figure 4). Z

t

I

65 pm

X

4

Figure 3. Battlement

3.0 mm model of splitting edge represented the crenels between them.

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by protruding

merlons and

4. Results and Discussion The computational fluid dynamics simulations agree qualitatively with the experimental images (Figure 4). Darker areas downstream correspond to regions of the splitting edge with high merlons, whereas the lighter areas correspond to crenel regions in the modeled splitting edge. Therefore, we conclude that roughness in the splitting edge results in non-uniform flow in the entry region, which manifests itself as striping of fluorescein concentrations downstream from the splitting edge.

A

5.0 mm

Figure 4. Modeled column integration plot through device exhibiting to rough edge at splitting point.

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5. Conclusions The work shown here demonstrates the importance of quality control in the fabrication of microfluidic devices. If laser ablation is to be used to fabricate devices of this nature, steps must be taken to reduce the edge roughness so that a uniform distribution can be achieved at the inlet. Two promising avenues for eliminating this problem are the optimization of laser cutting parameters and development of a post-cutting procedure to flatten the edges. Efforts to determine the maximum merlon height that can be tolerated are underway, as well as alternate cutting strategies to minimize the melting and pullback of the plastic at the splitting edge [7]. Quality control is a critical aspect in microtluidic device manufacturing and great caution must be exercised to avoid effects that are deleterious to device functionality. References D. Beebe; G. Mensing; G. Walker, Physics and up~~~cations of rn~cr~~u~dic~~in 1. biology, Annu. Rev. Biomed. Eng. 4:261-86 (2002). 2. B.H. Weigh P. Yager, Microjluidic d$,fkion-based separation and detection, Science, Jan; 283: 346-7 (1999). 3. J.P. Brody; P. Yager, D$Zusion-bused extraction in a micrqfabricated device, Sensors and Actuators A: Physical, 58: 13-l 8 (1997). 4. P. Jandik; B.H. Weigl; N. Kessler; 5. Cheng; C.J. Morris; T. Schulte; N. Avdalovic, Initial stu& of using a laminar,~~tid dijksion interface for sample prepamtion in high~~erformance liquid c~~romatogru~hy, J. Chromatography A. 954 (l-2): 33-40 (2002). J.P. Brody; P. Yager; R.E. Goldstein; R.H. Austin, Biotechnology at low Reynolds numbers, Biophysical J. 71: 3430-41 (1996). CR. Cabrera and P. Yager, Continuous concentration of bacteria in a ~~icr~~~~idic~o~~ cell using ekctrokinetic techniques, Electrophoresis, 22(2): 355-362 (2001). D.L. Pugmire; E.A. Waddell, R. Haasch; M.J.Tarlov; L.E. Locascio, Styface characterization o~laser-ab~ated~olymers used,for micro$uidics, Anal. Chem. 74(4): 871-8 (2002).

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