Vapor Phase Deposition of Functional Polymers onto Paper-Based

Oct 31, 2012 - Yong Shin Kim , Yuanyuan Yang , Charles S. Henry. Sensors ... Trinh Lam , Jasmine P. Devadhasan , Ryan Howse , Jungkyu Kim. Scientific ...
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Vapor Phase Deposition of Functional Polymers onto Paper-Based Microfluidic Devices for Advanced Unit Operations Philip Kwong and Malancha Gupta* Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, United States S Supporting Information *

ABSTRACT: Paper-based microfluidic devices have recently received significant attention as a potential platform for low-cost diagnostic assays. However, the number of advanced unit operations, such as separation of analytes and fluid manipulation, that can be applied to these devices has been limited. Here, we use a vapor phase polymerization process to sequentially deposit functional polymer coatings onto paper-based microfluidic devices to integrate multiple advanced unit operations while retaining the fibrous morphology necessary to generate capillary-driven flow. A hybrid grafting process was used to apply hydrophilic polymer coatings with a high surface concentration of ionizable groups onto the surface of the paper fibers in order to passively separate analytes, which allowed a multicomponent mixture to be separated into its anionic and cationic components. Additionally, a UV-responsive polymer was sequentially deposited to act as a responsive switch to control the path of fluid within the devices. This work extends the advanced unit operations available for paper-based microfluidics and allows for more complex diagnostics. In addition, the vapor phase polymerization process is substrate independent, and therefore, these functional coatings can be applied to other textured materials such as membranes, filters, and fabrics.

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allowing the smaller molecular weight analytes to diffuse perpendicular to the direction of flow into an adjacent coflowing stream. However, the design of this system required a significant increase in the size of the paper-based microfluidic device; the device could only isolate the lower molecular weight component, and large molecular weight differences were required. Switches have been recently used to control the path of fluid within paper-based microfluidic devices. For example, Martinez et al.18 and Li et al.19 fabricated switches that were activated by physically connecting different hydrophilic paper regions; however, this approach can be tedious or lead to nonreproducible flow profiles. Chen et al.20 fabricated switches using surfactants to reduce the surface tension of the diagnostic solution to allow the fluid to permeate hydrophobic barriers. However, operation of these devices required more complex designs with multiple inlets. It is difficult to incorporate advanced unit operations onto paper-based microfluidic devices because flow through these devices relies on capillary action rather than external pumping, and therefore, any modification of the paper substrate must not affect the fibrous morphology.8 The integration of multiple unit operations can be further complicated by the need to sequentially modify the paper substrate for each function. Here, we use initiated chemical vapor deposition (iCVD) to

icrofluidic devices have received significant attention for applications in diagnostics, primarily in resource-limited settings, because they require low volumes of reagents and are easy to transport and store.1−3 While traditional microfluidic devices have been fabricated from polymers such as poly(dimethyl siloxane)4,5 and poly(methyl methacrylate),6,7 paperbased microfluidic devices have recently emerged as an excellent platform for diagnostic applications due to their numerous advantages, including low-cost of fabrication and minimal equipment requirements.8,9 Paper-based microfluidic devices are easily fabricated by printing and melting hydrophobic wax into hydrophilic porous chromatography paper.9,10 A number of recent papers have highlighted the current and potential advantages and capabilities of paper-based microfluidic devices.11−13 Despite the numerous advantages of paper-based microfluidic devices, one potential drawback is that the development of advanced unit operations, such as separation of analytes and fluid manipulation, that are ubiquitous in polymer-based microfluidics has been challenging,14,15 and only a few systems have been demonstrated. For example, Carvalhal et al.16 separated uric acid from ascorbic acid by altering the pH of the diagnostic solution to reduce the solubility of uric acid which led to chromatographic separation on unmodified cellulose while Yang et al.17 spotted antibodies onto paper to agglutinate red blood cells in order to separate plasma from whole blood. Both of these techniques are highly specific and cannot be universally extended to other systems. More generally, Osborn et al.14 separated analytes of different molecular weights by © 2012 American Chemical Society

Received: October 2, 2012 Accepted: October 31, 2012 Published: October 31, 2012 10129

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buffers at pH 4, pH 6, pH 8, and pH 10 (BDH, ACS grade) were used as received without further purification. Polymer depositions were performed in a custom-designed pancake-shaped iCVD vacuum chamber (GVD corporation), as described previously.26 The pressure was maintained using a rotary vane vacuum pump (Edwards E2M40) and controlled using a throttle valve (MKS 153D). The initiator flow rate was controlled using a mass flow controller (MKS 1479A), and the monomer flow rate was controlled by heating the monomer source at a constant temperature. A nichrome filament array (Omega Engineering, 80%/20% Ni/Cr) was resistively heated to 270 °C to decompose the initiator into radicals. The reactor stage was kept at a constant temperature using a back-side recirculating heat exchanger. The thickness of the polymer coatings was measured on reference silicon wafers using a 633 nm helium−neon laser interferometry system and determined to be approximately 100 nm for both the gPMAA and gPDMAEMA coatings. For the deposition of poly(methacrylic acid-co-ethylene glycol dimethacrylate)-g-poly(methacrylic acid) (gPMAA), we first deposited poly(methacrylic acid-co-ethylene glycol dimethacrylate) (xPMAA) for 9 min followed immediately by deposition of poly(methacrylic acid) (PMAA) for 7 min. To deposit the xPMAA layer, the pressure of the reactor was maintained at 250 mTorr, the initiator flow rate was 0.6 sccm, the MAA was kept at room temperature and had a flow rate of 13.4 sccm, the EGDMA was heated to 55 °C and had a flow rate of 0.5 sccm, and the stage was maintained at 25 °C. To deposit the PMAA layer, the conditions described above were used without EGDMA. Residual ungrafted PMAA was removed by repeatedly washing samples in deionized water. For Fourier transform infrared (FT-IR) spectroscopy analysis, depositions of xPMAA were extended to 20 min to achieve thicker samples for analysis. For the deposition of poly(dimethylaminoethyl methacrylate-co-ethylene glycol dimethacrylate)-g-poly(dimethylaminoethyl methacrylate) (gPDMAEMA), we first deposited poly(dimethylaminoethyl methacrylate-co-ethylene glycol dimethacrylate) (xPDMAEMA) for 10 min followed immediately by deposition of poly(dimethylaminoethyl methacrylate) (PDMAEMA) for 10 min. To deposit the xPDMAEMA layer, the pressure of the reactor was maintained at 150 mTorr, the initiator flow rate was 0.6 sccm, the DMAEMA was kept at room temperature and had a flow rate of 6.0 sccm, the EGDMA was heated to 40 °C and had a flow rate of 0.3 sccm, and the stage was maintained at 22 °C. To deposit the PDMAEMA layer, the conditions described above were used without EGDMA. Residual ungrafted PDMAEMA was removed by repeatedly washing samples in deionized water. For FT-IR analysis, depositions of xPDMAEMA were extended to 30 min to achieve thicker samples for analysis. For the deposition of poly(o-nitrobenzyl methacrylate) (PoNBMA), the pressure of the reactor was maintained at 60 mTorr, the initiator flow rate was 0.6 sccm, the oNBMA was kept at 80 °C and had a flow rate of 0.1 sccm, and the stage was maintained at 30 °C. The deposition proceeded for 5 min. FT-IR was performed using a Thermo Scientific Nicolet iS10 spectrometer. X-ray photoelectron spectroscopy (XPS) was performed using a Surface Science Instruments M-Probe spectrometer with a monochromatic Al Kα X-ray source. High-resolution scans of the C 1s region were acquired with a resolution of 0.065 eV. Low-resolution survey scans were acquired at binding energies between 1 and 1000 eV with a

deposit polymer coatings onto paper-based microfluidic devices to integrate multiple advanced unit operations onto a single device. The iCVD process is a solvent-free process that allows for deposition of thin conformal polymer coatings onto nonplanar substrates such as electrospun fiber mats21,22 and membranes23 because of the lack of surface tension effects such as dewetting and clogging.24 The use of the iCVD process allows us to modify the surface properties of paper-based microfluidic devices while retaining the fibrous morphology necessary to generate capillary-driven flow, and therefore, multiple unit operations can be integrated onto one device, the size of the device remains unaltered, and the amount of additional equipment required is minimized. Furthermore, the iCVD process allows for the patterning of polymer coatings onto chromatography paper,25,26 which is useful for the incorporation of additional functionality. In this paper, we used iCVD to deposit acidic poly(methacrylic acid) (PMAA) and basic poly(dimethylaminoethyl methacrylate) (PDMAEMA) as ion-exchange coatings to separate analytes on the device. In contrast to the separation techniques described above, ion-exchange chromatography can be generally applied to a wide variety of systems such as for protein separation27,28 and water purification.29,30 While thin-layer chromatography (TLC) is often used to separate analytes because of its compatibility with organic and corrosive solvents and ability to achieve high resolution,31 the use of inflexible TLC plates is not well suited for the incorporation of other unit operations, such as three-dimensional multiplexing,32 thus limiting its potential for lab-on-a-chip applications. Additionally, TLC plates are more expensive than chromatography paper, making the design of low-cost diagnostic TLC systems less achievable. We fabricated a single paper-based microfluidic device with multiple integrated unit operations by sequentially depositing poly(onitrobenzyl methacrylate) (PoNBMA) as a UV-responsive switch. This device can be used for multistep processes, such as assays which require incubation.20 The ion-exchange coatings were composed of two layers: a cross-linked layer that is insoluble in aqueous solvents and a grafted homopolymer layer that improves the wettability and increases the number of ionizable groups on the surface. This allowed for selective separation of cationic and anionic analytes from a multicomponent mixture. The hydrophobic PoNBMA switch was activated by exposure to UV light, which renders the polymer hydrophilic, allowing aqueous fluid to pass through the polymer region. Our iCVD modification process advances the current capabilities of paper-based microfluidics by allowing for the analysis of more complex mixtures and the performance of assays that require separations or external control over the path of fluids. Additionally, the use of ionizable polymer coatings enables the development of other advanced pH-responsive unit operations to control the release of specific analytes, which is useful for signal amplification and multistep processes.14,33

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EXPERIMENTAL SECTION Methacrylic acid (MAA) (Aldrich, 99%), dimethylaminoethyl methacrylate (DMAEMA) (Aldrich, 98%), ethylene glycol dimethacrylate (EGDMA) (Aldrich, 98%), o-nitrobenzyl methacrylate (oNBMA) (Polysciences, 95%), t-butyl peroxide (TBPO) (Aldrich, 98%), toluidine blue O (Aldrich, 80%), crystal violet (Aldrich, 90%), methyl orange (Aldrich, 85%), ponceau S (Aldrich, 75%), tartrazine (Aldrich, microscopy grade), brilliant blue G (Aldrich, microscopy grade), and 10130

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Figure 1. FT-IR spectra of (a) xPMAA and (b) xPDMAEMA, high-resolution carbon 1s XPS spectra of (c) PMAA and xPMAA, and XPS survey spectra of (d) PDMAEMA and xPDMAEMA.

in triplicate. The Rf and capacity factor (k′ = (1 − Rf)/Rf) values are tabulated in Tables S-1 and S-2 in the Supporting Information, respectively. Multicomponent separations were performed by combining 0.5 mg/mL solutions of toluidine blue O and ponceau S at pH 4. The solution was spotted, and separation was analyzed as described above. For the fabrication of a UV-responsive PoNBMA switch, PoNBMA was first deposited conformally over the paper, as described above. The paper channels were masked, and the remaining channel was exposed to UV light for 3 h (UVP, 254 nm, 6 W), washed in deionized water, and dried in atmosphere. To activate the switch, the entire channel was exposed to UV light for 1 h, which rendered the polymer zone hydrophilic.

resolution of 1 eV. Data analysis was performed using the ESCA25 Analysis Application (V5.01.04) software. Paper-based microfluidic devices were produced by printing wax (Xerox Phaser 8560N) onto chromatography paper (Whatman, grade 1) and subsequently melting the wax through the depth of the paper in an oven at 180 °C for 3 min.9,10 The thickness of the paper was approximately 180 μm. The inner dimensions of the channels were 50.0 mm in length and 5.0 mm in width prior to melting of the wax and 48.8 mm in length and 3.6 mm in width after melting of the wax. Static contact angles were measured on paper coated with polymer using a contact angle goniometer (Ramé-Hart model 290-F1). The contact angle of a 5 μL drop of deionized water was measured at its equilibrium value, which was normally achieved within 3 min. Lateral flow rates were measured by suspending paper channels in a saturated water environment to prevent evaporative loss. Both static contact angles and lateral flow rates were performed in triplicate. The morphology of unmodified paper and the paper coated with polymer was analyzed using a JSM 7001F scanning electron microscope. Analysis of the separation ability of paper devices coated with gPMAA and gPDMAEMA was performed by spotting a 0.5 mg/mL buffered solution of dye at the pH of interest onto the channels and allowing them to dry under ambient conditions. The samples were then placed with one end in a reservoir of buffer solution in a saturated water environment such that the buffer solution wicked vertically upward through the paper channel. The migration distance of the dye relative to the migration distance of the buffer, known as the retardation factor (Rf), was used to quantify the separation ability of each polymer coating. Determination of the Rf values on paper channels without wax barriers yielded similar values to those measured on channels with wax barriers. Therefore, channels with wax barriers were used as this is currently the most common method for making paper-based microfluidic devices and ensures that our work can be extended to more complex devices where wax barriers are required to direct fluid flow into multiple paths. Separation analysis of each dye was performed

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RESULTS AND DISCUSSION The iCVD process was used to deposit acidic PMAA and basic PDMAEMA onto paper-based microfluidic devices to act as ion-exchange coatings and enhance separations. The carboxylic acid groups of PMAA are readily deprotonated in basic solutions which generates anionic moieties, while the tertiary amine groups of PDMAEMA become protonated in acidic solutions which generates cationic moieties. For practical applications, it is important to prevent the dissolution of PMAA and PDMAEMA in aqueous solutions. Therefore, the coatings were cross-linked by the addition of ethylene glycol dimethacrylate (EGDMA) during the deposition process to generate insoluble poly(methacrylic acid-co-ethylene glycol dimethacrylate) (xPMAA) and poly(dimethylaminoethyl methacrylate-co-ethylene glycol dimethacrylate) (xPDMAEMA). The flow rate of the EGDMA cross-linker was varied to try to minimize the amount of EGDMA in the polymer coatings in order to increase the number of ionizable groups on the surface. EGDMA flow rates lower than 0.5 sccm for xPMAA and 0.3 sccm for xPDMAEMA led to polymer films that dissolved in aqueous solutions. Fourier transform infrared (FT-IR) spectroscopy was used to confirm the chemical structure of the insoluble xPMAA and xPDMAEMA coatings, as shown in Figure 1. The spectrum of xPMAA (Figure 1a) was consistent 10131

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on paper limited the lateral flow rate of water through the paper and limits the practicality of xPMAA and xPDMAEMA for paper-based microfluidic applications. In an effort to produce more hydrophilic polymer coatings, PMAA and PDMAEMA homopolymers were grafted onto their respective cross-linked polymers using a process previously developed by Ye et al. to graft antimicrobial iCVD polymer coatings.39 They hypothesize that grafting occurs by polymerization to unterminated radicals on the surface of the cross-linked layer. In order to produce hydrophilic coatings, PMAA and PDMAEMA were deposited immediately after deposition of their respective cross-linked copolymers leading to the fabrication of poly(methacrylic acidco-ethylene glycol dimethacrylate)-g-poly(methacrylic acid) (gPMAA) and poly(dimethylaminoethyl methacrylate-co-ethylene glycol dimethacrylate)-g-poly(dimethylaminoethyl methacrylate) (gPDMAEMA), respectively, as shown schematically in Figure 2. Additional ungrafted PMAA and PDMAEMA chains were removed by repeatedly washing the paper in water. The gPMAA coating contained a significantly higher amount of MAA (MAA/EGDMA ∼6.0) on the surface compared to xPMAA (MAA/EGDMA ∼0.6) as determined by comparing the relative area of the carboxyl and ester carbon to the carbon singly bound to oxygen in the C 1s XPS spectrum, which is consistent with grafting of PMAA to xPMAA. Similarly, the gPDMAEMA coating (atomic ratios of carbon, nitrogen, and oxygen of 67%, 5%, and 28%, respectively, as determined by XPS) had a higher DMAEMA to EGDMA ratio (DMAEMA/ EGDMA ∼2.2) than the xPDMAEMA coating (DMAEMA/ EGDMA ∼0.5), which is also indicative of successful grafting. Analysis of the paper coated with gPDMAEMA indicated nitrogen was present in similar atomic ratios on both the top and bottom sides of the paper, demonstrating that the polymer conformally coated through the depth of the paper. The grafting process increased the hydrophilicity of the polymer coatings relative to the cross-linked polymers as demonstrated by a decrease in the static contact angle and increase in the lateral flow rate of water through the coated paper (Table 1). While the lateral flow rates of water through channels coated with either gPMAA or gPDMAEMA were lower than through uncoated paper, the flow rates were sufficient for practical paper-based microfluidic applications. In addition to increasing the hydrophilicity of the polymer coatings, the grafting process also increased the surface concentration of ionizable MAA and DMAEMA moieties which should lead to improved separation. The scanning electron microscopy images shown in Figure 3 demonstrate that the gPMAA and gPDMAEMA coatings did not occlude the pores allowing for the retention of the fibrous morphology that is important to generate capillary driven flow. The ability of paper-based microfluidic devices coated with either gPMAA or gPDMAEMA to separate analytes based on electrostatic interactions was studied as a function of the pH of the diagnostic solution using organic dyes as model analytes. The degree of separation was determined by the relative ratio of the migration distance of the dye to the migration distance of the solvent front, known as the retardation factor (Rf). The value of Rf on coated paper channels was compared to uncoated paper channels to account for any changes in dye solubility as a function of pH, and the results are shown in Figure 4. It should be noted that cellulose displays electronegative hydroxyl groups although significant deprotonation is not expected at pH values less than 10.40 Toluidine blue O and crystal violet were used as model cationic analytes. The paper channels coated with gPMAA

with incorporation of both methacrylic acid (MAA) and EGDMA into the polymer coating. The broad band at 3500 cm−1 is attributed to the hydroxyl moiety of MAA; the weak absorbance at 1623 cm−1 is attributed to the vinyl stretching vibration from partially unreacted EGDMA units, and the weak absorbances at 2975 and 2950 cm−1 and the strong absorbance at 1720 cm−1 are attributed to the stretching vibrations of the aliphatic and carbonyl moieties, respectively, of both MAA and EGDMA.34,35 Similarly, the spectrum of xPDMAEMA (Figure 1b) was consistent with incorporation of both dimethylaminoethyl methacrylate (DMAEMA) and EGDMA into the polymer coating. The weak absorbance at 2760 cm−1 is attributed to the tertiary amine of DMAEMA; the weak absorbance at 1623 cm−1 is attributed to the vinyl stretching vibration from partially unreacted EGDMA units, and the weak absorbances at 2975 and 2950 cm−1 and the strong absorbance at 1726 cm−1 are attributed to the stretching vibrations of the aliphatic and carbonyl moieties, respectively, of both DMAEMA and EGDMA.36,37 X-ray photoelectron spectroscopy (XPS) further confirmed the structure of the polymer coatings and was used to determine the relative amount of EGDMA in both the xPMAA and xPDMAEMA coatings. Figure 1c shows the high-resolution carbon 1s spectra of PMAA and xPMAA. For PMAA, the carbon environments at 282 and 286 eV are attributed to carbon bound only to other carbon (C−C) or hydrogen (C−H) and carboxyl carbon (COOH), respectively.38 For xPMAA, the ester carbon (COOR) of EGDMA overlaps with the carboxyl carbon of PMAA at 286 eV, while the carbon singly bound to oxygen (C−O) of EGDMA appears at 284 eV.38 The ratio of MAA to EGDMA in the xPMAA coating was determined by comparing the relative area of the carboxyl and ester carbon to the carbon singly bound to oxygen and was found to be 0.6. Figure 1d shows the survey spectra of PDMAEMA and xPDMAEMA which is characterized by the carbon 1s peak at 284 eV, the nitrogen 1s peak at 399 eV, and the oxygen 1s peak at 531 eV. The PDMAEMA coating had experimental atomic ratios of carbon, nitrogen, and oxygen of 71%, 6%, and 23%, respectively, which is in relatively close agreement with the theoretical values of 73%, 9%, and 18%, respectively. Conversely, the xPDMAEMA coating had atomic ratios of 73%, 2%, and 25% for carbon, nitrogen, and oxygen, respectively. The ratio of DMAEMA to EGDMA in the xPDMAEMA coating was determined by comparing the relative atomic ratios of nitrogen to oxygen and was found to be 0.5. While cross-linking rendered the polymer films insoluble in aqueous solutions, it also led to an increase in the hydrophobicity of the paper surface as observed by an increase in the contact angle as summarized in Table 1. The high contact angle Table 1. Contact Angle and Lateral Flow Rate Data of Uncoated and Coated Papera polymer coating

contact angle (deg)

lateral flow rate (mm/min)

uncoated xPMAA gPMAA xPDMAEMA gPDMAEMA

0 102 ± 5 0 96 ± 5 0

12.8 ± 2.0 0 6.4 ± 0.8 0 2.5 ± 0.3

a

Grafted coatings demonstrate an increased hydrophilicity relative to cross-linked coatings. 10132

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Figure 2. Schematic of the grafting process. Cross-linked polymer is deposited onto the paper fibers followed by deposition of homopolymer, which results in grafting. Additional ungrafted homopolymer is removed by repeatedly washing the paper in water.

uncoated channels due to the gPDMAEMA coatings bearing less electronegative functionality than cellulose. Tartrazine and ponceau S were used as model anionic analytes. The channels coated with gPDMAEMA exhibited significantly improved separation of the anionic analytes at acidic pH values but comparable or poorer separation at basic pH values. This is attributed to protonation of the gPDMAEMA (pKa value of ∼8)45 only at more acidic pH values which significantly increases the electrostatic interaction between the cationic gPDMAEMA and the anionic analytes. Conversely, the paper channels coated with gPMAA demonstrated comparable separation of the anionic analytes relative to the uncoated channels due to the fact that both gPMAA and cellulose do not display significant electropositive functional groups. Methyl orange and brilliant blue G were used to model amphoteric analytes that contain both acidic and basic functional groups. The channels coated with gPDMAEMA demonstrated moderately improved separation. This suggests that these amphoteric analytes display an overall anionic character which is attributed to the presence of the highly electronegative sulfonic acid groups. Similar to the separation of the anionic analytes, the separation of these amphoteric analytes on the channels coated with gPDMAEMA is pH dependent with improved separation at more acidic pH values. The two dyes

Figure 3. SEM images of (a) uncoated paper, (b) paper coated with gPMAA, and (c) paper coated with gPDMAEMA.

demonstrated improved separation (lower Rf values) relative to the uncoated channels, leading to almost complete partitioning of the analytes to the stationary phase. This is attributed to an increased electrostatic attraction between the cationic dyes and the electronegative carboxylic acid groups of gPMAA. The effect of pH on the separation ability of gPMAA is negligible despite PMAA having a pKa value of approximately 5.5.41 This may be due to partial ionization of the gPMAA at pH 442 as well as increased hydrogen bonding effects43,44 as the degree of ionization of the gPMAA decreases. Alternatively, the paper channels coated with gPDMAEMA generally demonstrated slightly worse separation (higher Rf values) relative to the

Figure 4. Rf values of (a) toluidine blue O, (b) crystal violet, (c) tartrazine, (d) ponceau S, (e) methyl orange, and (f) brilliant blue G on uncoated paper channels (blue diamond), paper channels coated with gPMAA (green triangle), and paper channels coated with gPDMAEMA (red square). 10133

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behaved differently on channels coated with gPMAA, with the separation of methyl orange on channels coated with gPMAA being comparable to separation on uncoated channels and separation of brilliant blue G on channels coated with gPMAA being significantly reduced at more basic pH values. It is possible that amphoteric analytes which display more electropositive character will show reduced separation on gPDMAEMA coatings and improved separation on gPMAA coatings. We demonstrated the applicability of these coatings for paper-based microfluidic applications by separating analytes from a multicomponent mixture. Figure 5 shows the effect of Figure 6. (a) Deposition and patterning of a UV-responsive switch onto microfluidic channels coated with gPMAA. The switch is patterned by masking a portion of the channel during exposure. (b) Activation of the switch and subsequent separation of toluidine blue O and ponceau S.

can be activated by exposing the PoNBMA region to UV light, allowing for aqueous fluids to travel up the length of the channel and subsequently allow analytes to be separated by the ion-exchange coating. While the response time of the PoNBMA switch is approximately 1 h, this can be reduced using a higher intensity UV light. Figure 6b demonstrates the controlled separation of toluidine blue O and ponceau S on gPMAA after activation of the switch.

Figure 5. (a) Applied mixture of toluidine blue O and ponceau S on an uncoated channel and separation on (b) an uncoated channel, (c) a channel coated with gPMAA, and (d) a channel coated with gPDMAEMA. Arrow depicts direction of fluid flow.

gPMAA and gPDMAEMA coatings on the separation of a mixture of cationic toluidine blue O (blue) and anionic ponceau S (red) at pH 4. Initially, the applied dye is purple due to a combination of the individual dyes (Figure 5a). On uncoated paper channels (Figure 5b), the two dyes move at approximately the same speed and the dye area remains purple. On paper channels coated with gPMAA (Figure 5c), the polymer coating separates the cationic toluidine blue O, resulting in the red ponceau S flowing upward from the toluidine blue O. On paper channels coated with gPDMAEMA (Figure 5d), the reverse case is observed where the cationic polymer separates the anionic ponceau S resulting in the toluidine blue O flowing upward from the stationary red ponceau S. This demonstrates the ability to selectively separate either anionic or cationic analytes from a mixture of components and could easily be extended to biologically relevant systems. The iCVD process allows us to apply polymer coatings without altering the morphology of the paper substrate, and therefore, multiple coatings can be deposited to integrate different unit operations onto a single device. We demonstrated this by sequentially applying coatings of gPMAA and PoNBMA onto a paper channel to integrate separation of analytes and fluid manipulation, respectively, as shown in Figure 6. PoNBMA is a hydrophobic polymer that is converted to hydrophilic PMAA upon exposure to UV light and has previously been deposited onto chromatography paper using the iCVD process.25 The response of PoNBMA to UV light allows for both patterning and real-time operation of the switch. The PoNBMA switch was patterned by exposure to UV light through a mask and washing in deionized water, revealing the underlying gPMAA coating, shown schematically in Figure 6a. The remaining hydrophobic PoNBMA region restricts aqueous solutions to the inlet portion of the channel only. The switch

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CONCLUSIONS

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ASSOCIATED CONTENT

The iCVD process was used to conformally deposit functional polymer coatings onto paper-based microfluidic devices to integrate multiple unit operations while retaining the morphology of the paper. Ionizable polymer coatings to enhance separations were composed of a layer of cross-linked polymer and a layer of homopolymer which was grafted onto the cross-linked layer. The grafting process was found to be necessary to increase the hydrophilicity of the polymer coatings in order to allow them to be used in paper-based microfluidic applications and also to increase the surface concentration of the ionizable groups to enhance separation. Chromatography paper coated with gPMAA and gPDMAEMA improved the separation of cationic and anionic analytes, respectively, relative to uncoated chromatography paper, and the ability to separate analytes from a multicomponent mixture was demonstrated. The ability to integrate multiple unit operations was demonstrated by sequentially patterning a UV-responsive switch onto the channels coated with ion-exchange coatings, allowing for control of the path of fluids. This work extends the available advanced unit operations for paper-based microfluidics and allows for more complex diagnostics and for external manipulation of fluids. Additionally, the pH-responsive nature of the ionizable coatings suggests that these coatings can also be used to control the release of analytes for signal amplification and multistep processes in paper-based microfluidic applications.14,33

S Supporting Information *

Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org. 10134

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Science Foundation Division of Civil, Mechanical, and Manufacturing Innovation Award Number 1069328, the National Sciences and Engineering Research Council of Canada Scholarship (P.K.), and the Alfred Mann Institute at the University of Southern California (P.K.). We thank the Molecular Materials Research Center of the Beckman Institute of the California Institute of Technology for use of their XPS.

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REFERENCES

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dx.doi.org/10.1021/ac302861v | Anal. Chem. 2012, 84, 10129−10135