Enhancing Capillary-Driven Flow for Paper-Based Microfluidic

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Enhancing Capillary Driven Flow for Paper-based Microfluidic Channels Joel Songok, and Martti Toivakka ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b08117 • Publication Date (Web): 18 Oct 2016 Downloaded from http://pubs.acs.org on October 18, 2016

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ACS Applied Materials & Interfaces

Enhancing Capillary Driven Flow for Paper-based Microfluidic Channels Joel Songok*, Martti Toivakka Laboratory of Paper Coating and Converting and Center for Functional Materials, Abo Akademi University, Porthaninkatu 3, 20500 Åbo/Turku, Finland *Corresponding Author: Tel. +358 2 215 4232; email: [email protected] Abstract: Paper-based microfluidic devices have received considerable interest due to their benefits with regards to low manufacturing costs, simplicity and the wide scope of applications. However, limitations including sample retention in paper matrix and evaporation as well as low liquid flow rates have often been overlooked. This paper presents a paper-based capillary-driven flow system that speeds up flow rates by utilizing narrow gap geometry between two parallel surfaces separated by a spacer. The top surface is hydrophobic while the bottom surface is a hydrophobic paper substrate with a microfluidic channel defined by a hydrophilic pathway, leaving sides of the channel open to air. The liquid flows on the hydrophilic path in the gap without spreading onto the hydrophobic regions. The closed channel flow system showed higher spreading distances and accelerated liquid flow. An average flow rate increase of 200% and 100% was obtained for the nanoparticle coated paperboard and the blotting papers used, respectively. Fast liquid delivery to detection zones or reaction implies rapid results from analytical devices. In addition, liquid drying and evaporation can be reduced in the proposed closed channel system. Keywords: Paper-based microfluidics, Surface flow, Parallel plates, Capillary-driven flow, Superhydrophobic, Microchannel

Introduction Paper as a substrate for microfluidic analytical devices has attracted considerable interest, since paper is light, disposable, lowcost, biocompatible and wicks liquid thereby eliminating the need for an external pump. The overlying purpose of fabricating paper-based analytical devices (µPADs) is to provide low-cost, environmentally friendly diagnostic tools that are suitable for point-of-care (POC) diagnosis, in environmental monitoring, health diagnosis, food safety, and within home-care settings.1-3 µPADs consist of channels in hydrophilic paper demarcated by walls of hydrophobic barriers or air which guide the sample to the detection zone that is loaded with detection reagents.4-6 Several methods have been proposed for fabricating channels on paper, ranging from relatively complex methods (e.g. photolithography7 to simple approaches such as wax printing.8 The methods can be broadly classified into physical and chemical methods. In physical techniques, the hydrophobic additive or ink is deposited on the paper to create a hydrophobic barrier, e.g. by wax printing, plotting, inkjet etching, flexographic printing, laser treatment, ink stamping, paper cutting and shaping, lacquer spraying, or screen printing. In chemical methods, chemicals are used to change hydrophilic fiber properties to hydrophobic, e.g. by photolithography, plasma treatment, inkjet printing, chemical vapor-phase deposition or wet etching. Comprehensive studies on the development of the fabrication methods can be found in recent review articles.9-12 µPADs have been demonstrated for a range of tests such as for pH, glucose, protein, cholesterol, pesticides and heavy metals.13-15 However, there is still a need for high volume, low cost fabrication approaches to produce devices that utilize small sample volumes and transfer samples rapidly. The devices should provide basic microfluidic operations such as flow delays, mixing, and valving similar to conventional microfluidic devices. Although excellent switches and valves exist in conventional microfluidics and thorough mixing can be achieved, power supply or external pressure is commonly required. In passive pumping, capillary action guides the liquid within the microfluidic systems. A number of µPAD demonstrators have shown precise sample delivery times and metering of sample volumes.16-21 For example, Toley et al. (2013) have shown that a delay in fluid progress can be attained by diverting fluid into an absorbent pad placed along the channel. Flow delays between 3 and 20 min were achieved depending on the length and the thickness of the absorbent material. In the absence of the pad, the liquid front wicks to 80 mm in 400 s. Slow flow rates may result in sample loss through evaporation and drying, and these, together with sample retention within the paper matrix, can lower the efficacy of a µPAD. Therefore, a rapid delivery of small sample volumes to the detection zones is advantageous.22 JahanshahiAnbuhi et al. (2012) showed that flow acceleration can be achieved by placing a paper in between flexible films.23 A 800 µm gap was created on each side of the paper. A flow time reduction from 2000 s to 150 s was achieved, which was attributed to the deformation of the flexible film by capillary forces and formation of a wedge at the advancing liquid front. Although a substantial speed-up was observed, a large sample volume (device was dipped into the solution) was needed. Because flow rate is controlled by channel size, porosity, intrinsic cellulose properties and permeability, as well as the liquid properties, a fabrication technique that allows for liquid to flow on paper surface (or in a gap) while maintaining simplicity, low-cost, ease-of-use and does not require an external pump would be favorable. Previously, we presented a method which showed liquid delivery on the surface of paper rather than inside it.24 The technique makes use of the photocatalytic property of TiO2 nanoparticles deposited on paper. First, a high-speed, roll-to-roll liquid flame spray process is used to coat the paper with the TiO2 nanoparticles, which convert the paper surface to a super-hydrophobic one. The superhydrophobicity is due to a thin carbonaceous layer on the nanoparticles originating from volatile organic species

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released from the paper by the heat. Subsequently, the TiO2-coated paper is exposed to UV irradiation through a photomask to generate hydrophilic channels. On depositing liquid on the hydrophilic channel, it spreads spontaneously on the paper surface. Transporting the liquid on paper surface minimizes the sample retention in the paper, and enables use of smaller sample volumes. However, liquid evaporation and drying out is still a potential drawback. In this work, we present a capillary-driven surface flow system that enables a rapid delivery of small fluid amounts as well as reduces the problems associated with evaporation and drying out of the liquid. The proposed system consists of parallel surfaces (top and bottom) separated by a spacer, which leaves the channel sides open to air. The bottom surface (i.e. flow channel) has a planar hydrophilic path confined by a hydrophobic barrier whereas the top surface is fully hydrophobic. In the subsequent section, we will refer to this set up as the closed channel flow system in contrast to the open channel system which lacks the hydrophobic top cover. Closing the system with the hydrophobic top cover changes liquid-air interface curvature at the advancing liquid front leading to an extra driving force for liquid flow thus increased liquid flow rate. Similar set up has been implemented in conventional microfluidic devices with silicon and glass substrates.25-29 This paper describes the closed system as a tool applicable for paper based microfluidic applications. We investigate the influence of different hydrophobic top covers, gap size, liquid volume and different liquids on the rate of liquid flow. We compare the flow dynamics in the closed channel flow system to the open channel system and also with different paper substrates. Finally, we demonstrate the applicability of this method in paper devices by carrying out a glucose-protein qualitative assay.

Materials and Methods Micro-flow channel (bottom surface): A commercially available pigment coated paperboard (200 g/m2, Stora Enso, Sweden) was coated with TiO2 nanoparticles in a continuous roll-to-roll process using the liquid flame spray (LFS) method. A detailed description of the LFS technique has been reported previously.30, 31 This technique involves spraying nano-sized particles on the surface of materials such as paper or metal at high temperature and at ambient pressure. When TiO2 is coated on paperboard, a thin, transparent superhydrophobic surface with nearly 150° water contact angle is obtained. Hydrophilic channels were created by exposing the highly hydrophobic, TiO2-coated paper to ultraviolet light (UVA 320-390 nm, 50 mW.cm-2) (Bluepoint 4 ecocure, Hönle UV technology, DE) for 30 min through a photomask. The photomask was created by cutting copy paper with the desired pattern. The pattern utilized in this study consists of a bulb connected to a channel. The measured width of the channels after UV irradiation was ca. 5% narrower than the width defined by the mask. Photo-patterning provides flexibility in the design and creation of complex flow patterns. Figure 1 shows schematically the fabrication procedure for making the top and bottom surfaces of the closed channel system. Whatman® grade 1 filter paper (Blotting_P1) and Tesorb speciality blotting paper (80 gm-2, Tervakoski Oy, Finland) (Blotting_P2) were also used a bottom surfaces for liquid flow comparison to TiO2-coated paperboard. The properties of paper substrates are in Table 1 below. Pore size data was measured using mercury porosimetry, basis weight and thickness was obtained from the suppliers’ data sheets. Calculated porosity was obtained using the expression:32 , % = ( − ( ⁄( × ×

Surface roughness and air permeability was measured using Messmer Parker Print-Surf™ (PPS-ME90) (Applied paper technology, INC. USA) and Lorentzen & Wettre (L&W) air permeance tester SE-166 (Kita, Sweden), respectively. Table 1: Properties of the paper substrates Modal pore diameter (µm) Porosity % Basis weight (g/m2) Thickness (µm) Calculated porosity % Roughness (µm) Air permeability (ml/min)

Paperboard 7 44 200 180 26.9 1.85 0.75

Blotting_P1 7 63 87 180 68.2 10.75 2630

Blotting_P2 5.5 59 80 145 63.7 10.05 2050

A 1 mm wide channel was printed on Blotting_P1 and Blotting_P2 using a wax printer (Xerox® colorqube™ 8580). The printed pattern was put in an oven for 2 minutes at 195°C so as to melt the wax. Because paper is porous, the wax penetrates into the paper resulting in well-defined flow boundaries. Hydrophobic surface (top surface): A superhydrophobic paper surface created by LFS deposition of TiO2 nanoparticles as described above, can be used as the top surface. However, to enable better visualization of the fluid dynamics, two hydrophobic and transparent top covers were prepared: 1. Polytetrafluoroethylene (PTFE, Sigma-Aldrich®, US) dispersion (60 weight % dispersion in water) coated onto a glass slide and 2. laboratory film (Parafilm M®, Bemis Company INC., US) tightly wrapped onto glass slide. The glass slides offered reinforcement to the films and allowed for easy observation and recording of liquid flow. A drop of the PTFE dispersion was spin-coated (KW-4A, Chemat Technology Inc., US) onto a glass slide (pre-acceleration for 3s at 600 rpm, and coating for 60s at 4000 rpm.) After the coating, the glass slide was pre-dried on a hot plate at 120°C for 3 minutes before being transferred to a microwave furnace (Phoenix™ Microwave furnace, CEM Corparation, US) for 1 hour of drying at


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360°C. Above 320°C PTFE melts, resulting in a thermal bond with the glass substance. The second top-cover was prepared by tightly enveloping one side of a glass slide with a paraffin film, and then heating it in an oven at 50°C to enhance the adhesion. The surface wettability by water, isopropanol-water mixture (IPAW) and glycerol-water mixture (GW) was characterized by contact angle measurements (KSV CAM 200, KSV Instruments Ltd., FI) using the Laplace equation fit for capillary pressure to the projected 5 µL droplet curvature. Contact angle hysteresis was determined using the tilted plate method. A 5 µl water droplet was placed on a horizontal plane, then the plane and camera (the entire contact angle instrument) was tilted. Contact angle hysteresis was obtained from the difference between the advancing contact angle and receding angle at the point when the droplet starts to slide down. Although the tilted plate method has its limitations, it is a qualitative technique appropriate to differentiate a high-hysteresis surface that the droplet tends to stick to and a low hysteresis surface, where the droplet tends to slide down.33 (a)

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Figure 1: Steps involved in fabricating a closed surface flow system (a) roll-to-roll deposition of TiO2 on paper by LFS technique, (b) UV irradiation through a mask, (c) a planar hydrophilic channel defined by superhydrophobic borders (white=hydrophilic, grey=hydrophobic), (d) Spin coating of PTFE, (e) drying of PTFE, and (f) hydrophobic top cover. Device assembly: The UV treated paper was mounted onto a flat surface using double-sided tape. Spacers and the hydrophobic cover was placed on top of the paper, and finally 4 glass slides on top to exert uniform pressure across the assembly. Figure 2 illustrates the assembled closed channel system. A digital SLR camera (Nikon D3200) fitted with a macro lens (Sigma 105mm EX DG) for high resolution imaging was used to record videos at a rate of 50 frames per second, corresponding to a time resolution of 0.02s. Continuous video recordings were used to determine the position of the advancing liquid meniscus. Three different liquids that covered a range of surface tensions and viscosities were tested: water (72 mN.m-1, 1 mPa.s), waterisopropanol mixture (48 mN.m-1, 1.7 mPa.s) and water-glycerol mixture (66mN.m-1, 8.5 mPa.s). A small amount of amaranth red dye was added to water to improve the visual contrast. Each measurement was repeated at least three times to assess variability in the results. Flow behavior through different gaps (50, 100, 150 and 200 µm) were tested. The video recordings were analyzed using the ImageJ software.34 A B

Hydrophobic cover

Paper surface Figure 2: (A) schematic of the assembled closed channel flow system. (B) Cross-sectional view of a closed channel flow system with 100 µm spacers. The height of the scale bar is 100 µm. Demonstration of paper based biochemical assay: Colorimetric glucose and protein assays were used to demonstrate the applicability of the closed channel flow system in µPADs utilizing the reagents used in 7, 35. A channel (1 mm wide and 50 mm long) was designed with detection points at both ends. Sample was deposited at the halfway point of the channel, from where it spread to test areas. The test zones (Whatman® filter paper, 3 mm diameter round cutouts) were loaded with chemical indicators for the respective colorimetric assay.7 For glucose indicator, 0.1 µl of 0.6M potassium iodide in water and equal volume of 1:5 horseradish peroxidase/glucose oxidase were pipetted to the test zone and dried under ambient conditions. For the protein test zone, 250mM citrate buffer, prepared using trisodium citrate dehydrate and citric acid, was pipetted to the test zone. A 3.3mM tetrabromophenol blue dissolved in 95:5 ethanol/water was added to the test zone then dried at ambient conditions. The sample for demonstration was a mixture of 7.5 µM bovine serum albumin (BSA) and 5 mM glucose solution. All the chemicals were purchased from Sigma Aldrich. The device was assembled as described above. A sample volume of 5 µl was used.

Results and discussion



Contact angle: Figure 3 (A) below shows water contact angle on paperboard, TiO2 coated paper and TiO2 coated paper after UV irradiation. When TiO2 is coated on paperboard, a contact angle rise is observed from 70° to nearly 150°. The superhydrophobicity has been attributed to a combination of the nanoparticle surface chemistry and the hierarchical surface roughness that enhances the water repellency. Irradiating UV to TiO2-coated paper, the contact angle drops to nearly 10°. It has been shown that the UV light promotes photocatalytic oxidation of the thin carbonaceous layer covering the TiO2 nanoparticles, thereby increasing the number of hydroxyl groups and wettability.36 Although Teisala et al. (2013) have shown that UV treated TiO2 coated paper can recover its hydrophobicity within 30 days (contact angle 140°) due to contamination of the surface, recent work by Valtakari et al. (2016) have demonstrated that the wettability change can be made permanent by wetting and subsequent drying of the channels.37, 38 Figure 3 (B) shows average static contact angles for paraffin film and PTFE coated surface. PTFE coating shows a water contact angle of 140° while the paraffin film an angle of 110°. The 10 % v/v isopropanol-water mixture (IPAW) and 50% v/v glycerol-water mixture (GW) show contact angles of 88° and 100° when deposited on paraffin film surface. This confirms that the test liquids do not spread on the top cover. 180

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Figure 3: (A) Apparent water contact angle of the paperboard as a function of time, before coating with TiO2, after TiO2 coating and after 30 minutes of exposure to UV light. (B) Liquid contact angle measurement of the top covers. The contact angle measurements were performed at room temperature using a 5 µl droplet. The results present an average of 3 parallel measurements. Microfluidic flow: The flow experiments were performed on straight hydrophilic paths, consisting of 2 mm wide channels connected to hexagonal bulbs. When a droplet is placed on the bulb, it is spontaneously pulled in between the paper surface and the top cover (TiO2 coated paper) due to capillary action. The bottom paper confines the liquid on the hydrophilic path without propagating sideways into the hydrophobic regions nor spreading on the hydrophobic top cover. Figure 4 A shows a closed channel flow system where paper is used both as top cover and bottom surface. The super-hydrophobic paperboard (top cover) prevents the liquid from spreading on the hydrophobic areas while allowing for liquid delivery. (See also supporting information for video showing liquid flowing under the top cover). An absorbent pad was used at the end of the channel so as to drain out the liquid from the channel and also from the inlet. The TiO2 coated paper is not transparent which impedes the recording of meniscus position as a function of time. Therefore, transparent hydrophobic top covers were used to investigate the behavior flow behavior in the closed channel flow system. Figure 4B clearly shows that the hydrophobic regions effectively curb the liquid within the channel. A B 1 cm

2 mm

Figure 4: The closed channel flow system fabricated on paperboard showing dyed water confined within the hydrophilic region. (A) Paper top cover and (B) paraffin film top cover. Figure 5 shows the position of the liquid front as a function of time for different gaps (50, 100, 150 and 200 µm gaps) in the closed channel system. At short times, faster flow rates were observed in 50, and 100 µm gaps. This is because in smaller gaps, the Laplace pressure that results from meniscus formation between the two parallel plates is high. Slower flow rates were observed in the larger gap (200 µm) due to reduced driving pressure. At long times, viscous drag in the channel behind the advancing liquid front becomes dominant and is higher in channels with smaller gaps. For this reason, reduction in flow rates is observed for the 50 µm gap as shown in Figure 5A. The paraffin film surface showed faster flow rates than the PTFE coated surface i.e. comparing Figure 5A to Figure 5B. This is because the paraffin film surface has a higher surface energy than the


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#

PTFE coated surface resulting in a higher Laplace pressure difference. The Laplace pressure, ∆", is given by ∆" = (%&'() + $

%&'(+ −

+$ ,

, where %&'() and %&'(+ are static contact angles on the top and bottom surface respectively. - is the liquid surface

tension and w and h are channel width and height respectively.29 In the derivation of the equation, it assumed that the shape of the liquid front is rectangular and also assumes that the sides bounded by air to have contact angle of 180°. Therefore, change in the contact angle of the top surface affects the pressure. Secondly, paraffin film and PTFE coated surfaces depicts different surface characteristic. Figure 6 shows advancing and receding contact angle for water droplet deposited on paraffin film and PTFE coated surfaces obtained by tilted plate method. Droplet deposited on the paraffin film surface started to slide down at tilt angle of nearly 20° with contact angle hysteresis angle ~6°. On contrary, the droplet stuck on the PTFE coated surface even when the plane was tilted to 95° (maximum tilt achieved with the instrument used). PTFE coated surface showed the so-called ‘rose petal effect’33 i.e. a high static water contact angle of 140° with strong water adhesion to PTFE coated surface with contact angle hysteresis close to 40°. Hierarchical surface roughness, contamination (during coating or drying) may have contributed to this phenomenon. The ‘sticky’ surface adds an extra resistance that lowers the liquid flow rates. Paraffin film was used in the subsequent section because it was simple to prepare and the liquid transfer was faster. The liquid flow rate in the 150 µm gap lags behind the 100 µm gap hence we infer that the best gap in the current system, in relation to maximum driving force and the viscous drag, lies in between 50 and 150 µm. Overall, the flow rate decreases in time since the constant capillary forces driving the flow are balanced by the increasing viscous drag as liquid is moving in the channel. 60

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Figure 6: Advancing and receding contact angle obtained by tilted plate method.



Figure 7 compares liquid delivery on open and in closed channel flow systems. A significant reduction in fluid delivery time can be observed for the closed channel system. This is due to an additional capillary force (meniscus force) generated from the curvature between the top cover and bottom wetting channel, which induces a pressure difference between the wetting (liquid) and non-wetting region (air between the surfaces). We carried out tests with three different fluids, to cover a range of surface tensions and viscosities: water, IPAW and GW. A previous study on capillary flow in open channels (Songok et al., 2014) showed that increased liquid viscosity resulted in decreased flow rate.24 The same conclusion can be drawn for closed channels. Interestingly, for the liquid with high viscosity, the difference between the open and closed channel flow is minimal despite the additional driving force in the latter. This supports the earlier findings with the open channel set up that the flow of liquids with high viscosity is controlled by viscous forces. For a low viscosity liquid, e.g. water, faster flow rates are observed in the closed channel (average velocity = 12 mms-1) when compared to the open channel (4 mms-1). A decline in flow rate and eventual termination of flow is due to the finite liquid volume (8 µl) deposited. The use of a hydrophobic top cover on the device appears beneficial, since it provides an extra driving force for liquid flow and may also impede the evaporation of liquid. water_Closed channel Water_Open channel IPAW_Closed channel IPAW_Open channel GW_Closed channel GW_ Open channel

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Figure 7: Higher flow rates are observed for the closed channels (100 µm gap) in comparison to the open ones. One of the desired features for paper-based microfluidic devices is the ability to transport small liquid volumes within short times. In this section we compare liquid flow in Blotting_P1 and Blotting_P2 to TiO2-coated paperboard described above. Figure 8A shows the position of liquid front as a function time on TiO2-coated paperboard, in Blotting_P1 and Blotting_P2 when 10 µl liquid volume is used. The influence of top cover, paper substrate and gap size can be observed. (See also Supporting Information for videos of liquid flow on the different papers through 100 µm gap.) Both the Blotting_P1 and Blotting_P2 exhibit somewhat faster flow rates in the closed channel flow systems (~1 mm/s) than in the open channel (~0.07 mm/s). This can be attributed to the additional capillary force induced by the hydrophobic top cover as discussed above. The paper properties appear to have an impact on the liquid flow dynamics. Paperboard shows the faster flow rate (50 mm in 6 s, i.e. average velocity of 8 mm/s) than the Blotting papers because liquid is transferred on the paper surface. The liquid transport on the surface is bolstered the paper properties: low porosity and smooth surface with high surface energy minimizes absorption into the paper. On contrary, since the Blotting_P1 and Blotting_P2 papers are porous, in addition to moving on the paper surface, the liquid absorbs and propagates through the fiber matrix (20 mm distance in 300 s, i.e. ~0.07 mms-1). The influence of gap size on flow dynamics varies depending on the properties of the paper, i.e. roughness, porosity and thickness. TiO2-coated paperboard shows a clear increase in flow rate when the gap is changed from 50 to 100 µm. This is because in a narrow gap high viscous drag forces slow down the flow. The Blotting_P2 shows only a small change in flow rates for 50 and 100 µm gaps. However, Blotting_P1 shows higher flow rates in the 50 µm gap than in the 100 µm gap. Blotting_P1 is thicker than the other papers, and therefore it can absorb more liquid. Due to absorption and limited liquid volume used i.e. 10 µl, there may only be enough liquid to fill the 50 µm gap but not sufficient to fill the 100 µm gap. The liquid flow in the 100 µm gap shows a slowdown at ca. 10 s with subsequent acceleration at ca. 100 s. We postulate that the liquid flows initially both through the paper matrix and in the gap between the paper surface and the top cover. However, liquid transport via the gap halts because of insufficient liquid, meanwhile, liquid transport through the paper matrix continues. In addition, the rough paper surface might lead to pinning of the meniscus. The flow in the gap accelerates again due to the swelling of paper, which makes the gap narrower. Although different papers have shown varied flow behavior, the closed channel flow system enhances flow for all the papers.


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Figure 8: (A) Comparison of the liquid front position as a function of time for different paper substrates for a 10 µl droplet. (B) The elution distance a 1 µl water droplet spreads on a 1 mm wide channel on different substrates. Average velocity is presented on the secondary axis. A gap of 100 µm was used. Figure 8B shows how far 1 µl volume of water can advance on the paperboard, and in the Blotting_P1 and Blotting_P2. Liquid spreads the furthest on the paperboard surface. This is because of the properties of paperboard (low porosity and low permeability) which do not favour liquid absorption but surface wetting. For the Blotting_P1 and Blotting_P2, the absorptive forces dominate over the surface flow, and bulk of liquid is absorbed and retained within the fibre matrix limiting the advancement to ca. 40% short off that of the paperboard. Introducing a top cover, 35% distance is gained as well as increased average velocity. The Blotting_P2 shows higher average velocity than Blotting_P1 because of the smaller pore diameter and higher density (grammage/thickness), which promotes liquid spreading on the surface over the simultaneous absorption. The flow stops due to the limited sample volume. On contrary for Blotting_P1, the small liquid volume is preferentially absorbed and the transfer takes place mostly within the paper matrix resulting in a slow flow and consequently low average velocity. Most investigations into paper-based microfluidic devices have used commercially available filter papers. For these, sample retention within the paperfluidic channel (in filter paper) and sample evaporation have been identified to lower the efficiency of devices because less than 50% of the sample volume reaches the detection area.22 In this work, we have shown that paperboard substrate can transfer liquid fast and on the surface. Combined with the closed channel flow system, the problems associated with liquid retention and evaporation can be reduced and is advantageous especially when meager sample volumes are available. A covered system also offers faster sample transfer than an open one. The effect of paper surface roughness and potential compression of the paper due to the loading the top cover with 4 glass slides was not considered. The effect of channel width on flow behavior was not studied in depth, but it does have an influence on the flow. Studies by Hong and Kim (2015) concluded that the effect of surface tension force at the hydrophilic-hydrophobic boundaries is substantial when the channel width is in the order of 1 mm.39 Control of fluid flow: Fluid flow control is of prime importance in most microfluidics devices for both active- and passive-driven flows. Mostly, reactions (either biological or chemical) require sufficient time to complete reactions and to achieve maximal



signals.40 Capillary driven flows are affected by the physico-chemical properties of the interfaces of the flow domain and the geometrical characteristic of channel. In the TiO2-nanoparticle coated paper-based system, the fluid flow control can be achieved by varying the surface energy along the channel. In our previous work, we have shown that the extent of conversion of TiO2 coated paperboard from super-hydrophobic to hydrophilic depends on exposure time.41 Figure 9 shows the time delay for different stripe lengths located 10 and 20 mm away from the liquid inlet. Here, a stripe is defined as region along the channel with lower surface energy than the main channel. The stripe is fabricated simultaneously as the main channel but the UV exposure time is limited.41 The results indicated that for a given stripe length, the location of the stripe on the channel has negligible influence on the flow delay (i.e. stripes positioned at 10 mm and 20 mm depict similar flow delay). However, the time delays are directly proportional to the stripe length. The flow slows in the stripe area since the lower surface energy provides lower driving wetting force for the flow. While we have demonstrated that flow delay can be achieved by changing the length of the stripe, other factors such as irradiation times that vary the surface energy, gap size and channel width can be applied in manipulation of the flow. Different positions

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Stripe length

16 12 20mm

8

10mm

4 0 0

2 4 Length of the stripe, mm

6

Figure 9: The delay times created by using different stripe lengths of lower surface energy than the main channel. Inserted is a scheme indicating the stripe length and different positions (not drawn to scale) Assay demonstration: A paper-based planar hydrophilic channel was used to implement a parallel colorimetric assay for glucose and protein. These types of assays are well-known in detecting excess of protein or glucose in urine. 5 µL mixed solution of 7.5 µM BSA and 5 mM glucose solutions was pipetted at the inlet and within the first minute a color change was observed. Figure 10 shows the parallel assay for glucose and protein at different times. The indicator changes color from orange to pale green within the first minute for protein assay and white to brown within the second minute for glucose. The indicator (tetrabromophenol blue) undergoes sequential color change from orange to pale green to blue indicating the presence of protein. The color change is due to the dissociation of phenolic hydroxyl groups at a constant pH.42 The glucose measurement employs enzymatic methodology: glucose oxidase catalyzes the conversion of glucose to gluconic acid and hydrogen peroxide. Peroxide is reacted with iodine complex with the help of a second enzyme, peroxidase, to form a brown oxidized compound.42 Filter paper was loaded with reagents because it offered large surface area and its neutrality suits pH sensitive detection. The demonstrator consumes small volume of liquid and results are available within minutes. Multiple detection zones can be created as illustrated in Figure 10B. The demonstrated assembly process may not suit as such high volume roll-to-roll fabrication, but alternatively, the reagent can potentially be printed together with nanocellulose onto the paperboard instead of using the filter paper. A 60 s

0s 120 s

180 s

240 s

600 s

B


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C

Figure 10: (A) Parallel assays for glucose and protein on the closed channel microfluidic system. (B) Demonstration of multiple detections along a channel. (C) A schematic of the parallel assay showing the detection zones and inlet.

Conclusion A closed channel microfluidic system was used to enhance flow dynamics in paper based devices. The closed channel flow system consists of parallel surfaces (top and bottom) separated by a spacer, with no sidewalls. Liquid advances spontaneously between the surfaces, confined in the planar hydrophilic pathway on the bottom surface without spreading sideways into the hydrophobic regions nor spreading on the top cover. The bottom surface has a hydrophilic path demarcated by hydrophobic barrier. This is created by coating paper with TiO2 nanoparticles in a roll-to-roll process and exposing the coated paper to UV light through a photomask. Hydrophobic substrates, TiO2-nanoparticle coated paper, paraffin film or PTFE coating, were used as the top surface. The Paraffin film and the PTFE coating are transparent which enabled recording of liquid flow on the channels and it also demonstrated the range of hydrophobicity for the top cover. A complete, flexible paper-based device can be produced utilizing existing paper converting processes. Coating of TiO2 on paper is carried out in a roll-to-roll process, laser etching may be used to create the channel and using existing lamination techniques to close channel. The closed channel flow system increases the spreading distance and accelerates the liquid flow. Speed-ups of 200% and 100% were obtained for the nanoparticle coated paper board and the blotting papers used herein, respectively. The improvements are attributed to the increased capillary force (meniscus force) created by the non-wetting top cover, which modifies the liquid-air interface curvature in the narrow gap. An optimal gap distance exists, and is determined by the balance of the flow driving wetting force and the viscous drag of the flow in the channel, both which increase as the gap distance is reduced. For the closed microfluidic paperboard system presented herein, the best gap distance was ca. 100 µm. The closed channel flow system offers several benefits including increased flow rates, lower liquid retention, lower sample evaporation and a smaller sample volume requirement when compared to traditional filterpaper based µPADs.

Supporting Information The videos recorded from the top view show the position of the meniscus spreading on the different substrates investigated. This material is available free of charge via internet at http://pubs.acs.org.

Acknowledgements The authors thank the International Doctoral Programme in Bioproducts Technology (PaPSaT) for research support and Tervakoski Oy, Finland for supplying us with the paper.

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Enhancing Capillary-Driven Flow for Paper-Based Microfluidic

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