Selective Detection of K+ by Ion-Selective Optode Nanoparticles on

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Cite This: ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX

Selective Detection of K+ by Ion-Selective Optode Nanoparticles on Cellulosic Filter Paper Substrates Yoshiki Soda, Hiroyuki Shibata, Kentaro Yamada, Koji Suzuki, and Daniel Citterio* Department of Applied Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan S Supporting Information *

ABSTRACT: This work describes the generation of plasticized poly(vinyl chloride)-based ion-selective optode (ISO) nanoparticles by a piezoelectric inkjet dispensing device. The monodisperse inkjet-generated particles (polydispersity index: 0.177) with an average hydrodynamic diameter of 202 nm are suitable for the highly reproducible deposition onto cellulosic filter paper substrates, resulting in paper-based analytical devices (PADs) for colorimetric cation detection, as demonstrated on the example of potassiumresponsive ISOs. In contrast to the deposition of ISO bulk membranes from organic solutions requiring specialized printing equipment, the ISO nanoparticles can be inkjet-deposited from aqueous dispersions by conventional office inkjet printing. The obtained ISO PADs showed highly reproducible (relative standard deviations of the hue mean values in the range of 0.06−0.83% for three independently fabricated batches) and immediate (t95% ≤ 1 min) response to + aqueous K+ solutions buffered at pH 7.4, with high selectivity over Li+, Na+, Ca2+, and Mg2+ (log Kopt K+,Mz+ ≤ −5.2 (Li ); −3.6 + 2+ 2+ (Na ); < −5.0 (Ca ); < −5.2 (Mg )). In addition, causes for the distinctively different response observed for ISO nanoparticles in the liquid phase and on paper substrates were considered. For this purpose, several parameters related to the cation exchange reaction mechanism of ISOs were experimentally evaluated, allowing to semiquantitatively discuss the paper substrate-specific response of ISOs. KEYWORDS: inkjet printing technology, paper-based analytical devices, ion-selective optode nanoparticles, colorimetric assay

I

detectable by paper-based colorimetric tests (e.g., proteins, metabolites, metal ions, pesticides, explosive compounds, pathogens),10−13 application to alkali metal ions remains relatively rare due to the absence of classical chromogenic indicators. Not surprisingly, the ISO sensing technique has been transferred to the colorimetric detection of alkali metals on paper substrates and other low-cost porous analytical platforms. Meyerhoff’s group has reported that sodium ions (Na+),14 anions (F−, Cl−),15 and polyions (protamine)16 are detectable by polymeric matrix- and plasticizer-free ISOs on filter paper substrates. In 2016, Capitan-Vallvey and co-workers demonstrated ISO-based potassium ion (K+) analysis on a cotton thread.17 Very recently, we showed the implementation of a classical plasticized PVC membrane-based ISO system for Na+ ion detection into a paper device with integrated pHbuffering function.18 This work demonstrates for the first time the application of ISO particles as colorimetric reagent for K+ sensing to a paperbased analytical platform. For this purpose, water-dispersible polymeric ISO nanoparticles were fabricated. In addition to fast colorimetric response (t95% ≤ 1 min), the small-sized nanoparticles (∼200 nm diameter) allow the inkjet-based deposition onto paper, which is known as a reproducible and

on-selective optodes (ISOs) have been known as a powerful sensing technique for ionic species since the 1990s.1 They allow optical detection of a specific ion of interest commonly based on a two-phase equilibrium reaction between an aqueous sample phase and the organic optode phase.2 Besides conventional membrane-type sensors typically prepared with poly(vinyl chloride) (PVC) or similar polymeric materials, particles have become an alternative configuration of ISOs.3,4 Relying on ionophores, both the membrane-type and particletype ISOs commonly enable highly selective detection of an ionic species. However, ISO particles allow for faster response times and the possibility of miniaturized sensing, owing to their large specific surface area and their small size compared to the membrane-type counterparts. Currently, a myriad of analytical applications of ISO particles has been demonstrated including intracellular imaging,5 drinking water testing,6 and flow cytometry.7 Despite the optical signals being in many cases visually observable as analyte concentration-dependent color changes, applications of ISO particles in colorimetric analytical systems are still relatively scarce. Since their first introduction by Whitesides and co-workers in 2007, an explosive growth of research on microfluidic paperbased analytical devices (μPADs) has been witnessed.8 Being in line with the required low-cost and simple-to-use criteria of μPADs, colorimetry is one of the most frequently applied detection modes for this new class of analytical platform.9 Although a wide range of analytical targets has become © XXXX American Chemical Society

Received: February 9, 2018 Accepted: April 2, 2018 Published: April 2, 2018 A

DOI: 10.1021/acsanm.8b00222 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX

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ACS Applied Nano Materials scalable fabrication technique for paper-based devices.19−21 Notably, the water-based ISO nanoparticle ink eliminates the use of volatile organic compounds in the ISO paper device fabrication process, in contrast to the previous reports on ISObased ion detection on low-cost porous substrates, where tetrahydrofuran (THF) and/or cyclohexanone have been used for ISO reagent deposition.14−18 As the matrix of the colorimetric ISO nanoparticles for K+ sensing, plasticized PVC has been employed rather than micelle-type nanospheres typically prepared with a surfactant such as Pluronic F-127,5,6,22−26 of which the physical stability in dry condition encountered on a paper substrate remains a point of concern. PVC-based, monodispersed ISO nanoparticles were fabricated by inkjet dispensing of the ISO reagent cocktail into an aqueous solution containing surfactant. Although a piezodriven dispensing system27 and manual pipetting28 have been previously used for ISO nanoparticle fabrication, these approaches suffered from relatively large particle diameter unsuitable for inkjet printing (10 μm)27 or polydispersity of the particle size requiring a filtering process.28 Alternative types of optical sensor particles with high physical stability due to the use of cross-linked sensing matrices have been reported,29−32 but their preparation is not practically achievable by an inkjet dispensing approach. The ISO nanoparticles developed in the current work can readily be inkjet-printed onto filter paper substrates by means of a common office printer, enabling simple and reproducible fabrication of a paper-based analytical device (PAD) for selective colorimetric K+ sensing. As the first report on the application of ISO nanoparticles to PADs, this work also investigates the paper platform-specific response behavior of the ISO nanoparticles compared to a liquid-phase K+ assay using the same material. By achieving shorter response times, the ISO particle PADs showed superior properties as compared to previously reported ISO-based devices on porous substrates,14−18 which holds a great promise to achieve more practicable point-of-need testing devices.

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was dispensed for 15 min into 10 mL of an aqueous solution of 0.1 wt % Brij-35 by means of a piezo-driven inkjet dispensing device (Picojet2000, Microjet Co, Ltd.) equipped with an 80 μm diameter single nozzle tuned to 70 μm droplet size and 2000 Hz firing frequency. ISO particles fabricated by freehand pipetting were prepared by pipetting 0.543 mL of the ISO cocktail into 10 mL of an aqueous solution of 0.1 wt % Brij-35 using a micropipettor. Dynamic light scattering (DLS) measurements to determine the hydrodynamic diameter of ISO particles were performed by a Zetasizer Nano ZS from Malvern Instrument Ltd. Field-emission scanning electron microscopy (FESEM) analysis was performed on a JSM-7600F microscope (JEOM). Transmission electron microscopy (TEM) analysis was performed on a Tecnai Spirit TEM microscope (FEI company, part of Thermo Fisher Scientific). Potassium Sensing on Filter Paper Substrate. Inkjet-generated ISO particles were deposited onto the filter paper in 50 printing cycles as 7 mm diameter spots using the EPSON PX-105 inkjet printer. For this purpose, the ISO particle dispersion filled in a commercial refillable cartridge was dispensed from the cyan and yellow ink cartridges (color printing mode with the RGB printing color value settings at 0, 255, 255 for cyan and 255, 255, 0 for yellow). When it exited the inkjet printer, the paper surface was exposed to a stream of hot air from a hair dryer after each single printing cycle before being refed into the printer. After 25 cycles were printed from each cartridge, the paper substrate was additionally left to dry for 30 min at room temperature. Potassium sensing on the paper substrate was performed by first soaking the ISO particle-printed paper for 5 min into 1 mL of a KCl sample solution prepared in a Tris-HCl buffer (pH 7.4, 10 mM). After excess sample solution was blotted, the ISO paper spot was scanned, and the numerical color intensity values on the RGB scale were analyzed by the ImageJ software. For the quantitative evaluation of the ISO response on the paper substrate, the hue value on the huesaturation-value (HSV) color coordinate was calculated from the obtained red, green, and blue (RGB) color values. The hue values at full deprotonation and full protonation of the chromoionophore were determined by exposure of paper substrates to 10 mM NaOH and 10 mM HCl solutions, respectively. Potassium Sensing in Liquid Phase. For K+ sensing in the liquid phase, the ISO particle dispersion was first fivefold diluted by water. Next, pH-buffered KCl samples (10 mM Tris-HCl at pH 7.4) at various concentrations and the diluted ISO particle dispersion were mixed in a 1:1 ratio. After 5 min, the absorbance of the mixture at 658 nm was measured with the microplate reader using a 96-well microplate. The absorbance values at full deprotonation and full protonation of the chromoionophore were determined by mixing the diluted ISO particle dispersions with 10 mM NaOH and 10 mM HCl solutions, respectively. For colorimetry-based data analysis using particle dispersions, the entire microplate was placed on the scanner and color scanned, and the obtained RGB data were converted into hue values.

EXPERIMENTAL SECTION

Materials and Instruments. N,N-Dimethylformamide (DMF, super dehydrated), dioctyl sebacate (DOS), valinomycin (ionophore), KCl, NaCl, CaCl2·2H2O, LiCl·H2O, MgCl2·6H2O, 0.1 M HCl, polyoxyethylene(23) lauryl ether (Brij-35), NaOH, KOH, citric acid, boric acid, and Na3PO4·12H2O were purchased from Wako Pure Chemical Industries. Chromoionophore I (CH1) and high molecular weight PVC were purchased from Sigma-Aldrich. Sodium tetrakis-[3,5bis(trifluoromethyl)phenyl]borate (NaTFPB; anionic additive) was purchased from Dojindo Laboratories. Tris(hydroxymethyl)aminomethane was purchased from Tokyo Chemical Industry Co, Ltd. Ultrapure water (>18 MΩ cm) was obtained from a PURELAB flex water purification system (ELGA, Veolia Water). Filter paper (Advantec 5C, Toyo Roshi Co., Ltd.) was cut into A4 size before use. Absorbance spectra were acquired with a Varioskan Flash multi spectra microplate reader (Thermo Fisher Scientific). An HM-30R pH meter (DKK-TOA Co., Ltd.) was used to measure the pH of solutions. A piezo-driven EPSON PX-105 office printer (Seiko Epson) was utilized to print ISO particles onto an A4 sheet of Advantec 5C filter paper. PowerPoint (Microsoft) was used to design the printing pattern of the ISO particle ink. The color change of the filter paper substrate was captured with a CanoScan 9000F Mark II scanner (Canon). Numerical color intensity values of the paper were measured by the image processing software ImageJ (National Institutes of Health). Preparation of ISO Particles for Potassium Sensing. PVC (8.63 mg), 17.25 mg of DOS, 2.30 mg of valinomycin, 1.83 mg of NaTFPB, and 0.60 mg of CH1 were dissolved in 0.575 mL of DMF. In the case of inkjet-generated ISO particles, the resulting ISO cocktail

+

Determination of KKexch and pKa. For the determination of the +

ion exchange constant in the absence of ionophore (KKexch) and the pKa value of the chromoionophore (CH1), ionophore-free nanoparticles were prepared according to the procedure described above from cocktails not containing valinomycin. Potassium hydroxide was dissolved in ultrapure water at various +

concentrations to prepare samples to determine KKexch values, and pH values were measured. Absorbance of the particle dispersion and the color intensity values were recorded as described in the previous sections. For the pKa determination, a buffer composed of citric acid, boric acid, and trisodium phosphate (with a total concentration of 25 mM) including 100 mM KCl was prepared at various pH values.

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RESULTS AND DISCUSSION Fabrication of Inkjet-Printable ISO Nanoparticles. Submicrometer-sized and monodispersed ISO particles were B

DOI: 10.1021/acsanm.8b00222 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX

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ACS Applied Nano Materials fabricated by means of the solvent-displacement method.33 Inkjet dispensing of a DMF solution of the ISO reagent cocktail into a stirred aqueous solution causes PVC deposition at the interface between the organic solvent and the water. Rapid diffusion of the water-miscible DMF into the water phase causes formation of the PVC-based ISO nanoparticles. In this process, the Brij-35 surfactant serves as a stabilizing agent of the resulting emulsion.34 In this work, a piezoelectrically actuated inkjet dispenser was employed to fabricate the ISO particles. Thanks to the high droplet size uniformity achieved by the inkjet printing technology, the resulting ISO particles showed narrow size distribution (polydispersity index: 0.177) with an average diameter of 202 nm (Figure S1a). Spherically shaped particles of similar size were also confirmed in TEM images (Figure S2). On the one hand, their size and monodispersion properties enable clog-free inkjet-printing of the as-fabricated ISO nanoparticle dispersion onto a filter paper substrate with an unmodified office inkjet printer (Figure 1a) without the need of

composition, with all compounds showing very high partition coefficients toward the organic phase (log P: DOS = 10,35 chromoionophore 1 = 13.1,36 valinomycin = 8.6,37 TFPB = 10.038), was applied. While the nanosize potentially results in a biased distribution of sensing reagents between the particle bulk and its surface, a significant leaking of reagents into the surrounding aqueous phase is not expected. Fabrication Reproducibility. The K+ response of the developed ISO nanoparticles was first investigated in the liquid phase. As presented in Figure 2a, increasing absorbance at 540

Figure 1. Images of a filter paper substrate after 50 cycles of inkjet printing of ISO nanoparticles under identical conditions (spot diameter 7 mm): (a) inkjet-generated ISO particles; (b) freehandgenerated particles. The sharpness was modified for improved visibility.

Figure 2. Response of ISO nanoparticles to K+ ions: (a) absorbance spectra of aqueous ISO particle dispersions in the presence of various KCl concentrations at pH 7.4; (b) colorimetric response to aqueous K+ solutions (pH 7.4) on filter paper substrate with inkjet-deposited ISO nanoparticles (each spot on a single paper strip was printed from independently fabricated batches of ISO nanoparticles); (c) absorbance-based (liquid phase) and (d) hue-based (paper substrate) response curves (solid line: theoretical curve fitting based on eq 2); markers and error bars reflect the average and standard deviations of three experiments performed using independently fabricated batches of ISO nanoparticles (aqueous dispersion) or printed single-use paper strips, each with three spots from three independently fabricated batches of ISO nanoparticles.

a filtering process to remove larger particles. On the other hand, ISO nanoparticles prepared by simple freehand pipetting of an identical ISO cocktail DMF solution resulted in increased polydispersity (polydispersity index: 0.240) and larger particle diameter (average diameter: 334 nm) as shown in Figure S1b of the Electronic Supporting Information. Despite passing the particle dispersion through a 1 μm pore size syringe filter when transferring to the ink reservoir, the use of the freehandgenerated ISO particles led to rapid nozzle clogging of the office printer, as evidenced by the faint overall blue color and the appearance of blank lines in the circular ISO spot printed on the filter paper (Figure 1b). For clog-free inkjet dispensing of particulate materials, the particle size should as a rule of thumb be less than one-hundredth of the printer nozzle orifice diameter39 (∼20 μm for the inkjet printer used in this work), which supports the fact that the inkjet-generated ISO particles are reproducibly printable. The composition of the resulting ISO particles in terms of sensing reagents for both the inkjet- and freehand-generated versions is assumed to be identical to that of the prepared ISO cocktail solution. Although there is no experimental hard evidence for the exact composition of the nanoparticles, there are other reports where nano-optodes have been prepared by pipetting a solution of known amounts of sparsely water-soluble sensing reagents dissolved in a water-miscible organic solvent into water and where reagent composition identical to the prepared organic solution has been assumed.6 The situation might be significantly different in cases where sensing reagents are doped into nanospheres after their fabrication. In the current approach, the “classical” plasticized PVC optode

nm and decreasing absorbance at 610 and 658 nm were confirmed with KCl concentrations between 0.1 μM and 0.1 M. To avoid the “exhaustive sensing mode”,40 where the target analyte ion is depleted from the sample solution phase by extraction into the ISO phase, the as-fabricated ISO particle dispersion was fivefold diluted with water. Figure 2c represents the absorbance values at 658 nm at various activities of K+, obtained from three independently fabricated batches of ISO nanoparticles. The small error bars are a strong indication of the high fabrication reproducibility of the inkjet-generated ISO particles. Importantly, the small error bars were maintained also in the case of the paper-based assay (Figure 2b,d), with the standard deviations of the hue value within the dynamic response range (log aK+ = −5 to ca. −1.5) being between 0.06− 0.83% for three independently fabricated batches. These results suggest high reproducibility of both the inkjet-based ISO nanoparticle preparation and their inkjet-based deposition onto the filter paper substrate. Paper Substrate-Specific Response Behavior of ISO Nanoparticles. In contrast to self-assembled micelle-type ISO nanospheres possibly undergoing disintegration upon solvent evaporation, PVC-based ISO nanoparticles are expected to maintain their physical integrity after deposition on a paper C

DOI: 10.1021/acsanm.8b00222 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX

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ACS Applied Nano Materials

protonated and deprotonated form of the chromoionophore, respectively. Figure 4a,b shows the sigmoidal ISO response curves obtained in the liquid phase and on paper substrates, respectively.

substrate. The SEM images of Figure 3 reveal the presence of spherically shaped nanoparticles entangled between the

Figure 4. K+-dependent response curves of ISO nanoparticles (a) in the liquid phase (based on absorbance data) and (b) on paper substrates (based on hue data); data and experimental conditions identical to the ones shown in Figure 2.

As expected from the fact of using diluted nanoparticle dispersions, the optical response curves shown in Figure 4 do not reflect an “exhaustive mode” behavior. The valinomycin/K+ ratio in the case of the liquid-phase experiment for a 1 μM KCl sample is ∼20:1, resulting in a degree of deprotonation (α) of 0.20 (Figure 4a). To further verify that the system investigated represents a classical equilibrium sensing mode, the valinomycin/K+ ratio was reduced to 2:1 by additional dilution of the ISO particle dispersion, leading to an α value of 0.22 (data not shown). The small increase in α is attributed to the experimental uncertainty for absorbance measurements in extremely diluted nanoparticle dispersions (Figure S3). Therefore, it can be concluded that the valinomycin/K+ ratio of 20:1 used in the liquid-phase experiments does not result in an exhaustive-mode optode response. When it comes to the paper platform, it is not possible to determine the exact actual amounts of sensing reagents in the system, since the volume of ink dispensed from the printer is not known. Considering the volume of ink consumed during the printing of multiple sensing spots on paper (154 sensing spots), a rough estimation of the amount of sensing reagents deposited was made. On the basis of this, the valinomycin/K+ molar ratio in the case of a 1 μM KCl sample amounts to ∼5:1, which is 4 times lower than for the liquid-phase experiments, where exhaustive response is not observed as explained above. Therefore, an exhaustive sensing mode can be excluded under the experimental conditions applied for both the solution- and paper-based experiments. The Kexch values for the liquid phase and the paper substrate (Table 1) were obtained by fitting of the experimentally obtained data shown in Figure 4 to eq 2. Note that α values obtained from absorbance and from hue color coordinates are similar but not necessarily identical.41 When working with paper-based devices, absorbance measurements are not readily achievable in contrast to hue values. For this reason, hue-based

Figure 3. SEM images of (a) unmodified filter paper and (b−d) inkjetgenerated ISO particles deposited on a filter paper substrate by inkjet printing.

cellulosic fibers of the paper. The formation of a continuous membrane phase due to particle fusion can be excluded. Therefore, the response behavior of the ISO nanoparticles can basically be assumed to be identical in the liquid phase and on the paper substrate. To evaluate this assumption, comparison studies on the ISO nanoparticle response behavior in the liquid phase and on paper substrates were performed. The ISO response mechanism is based on the exchange of target ions (K+) and protons (H+) between the aqueous sample solution phase and the organic optode phase initially containing ionophore (L), chromoionophore (C), and anionic additive (R−). The overall process can be described by the equilibrium reaction according to eq 1: K+ (aq) + L (org) + CH+ (org) + R− (org) ⇄ KL+ (org) + C (org) + H+ (aq) + R− (org)

(1)

+

The K activity-dependent (aK+) response of an ISO is represented by the following equation:1 RT − (1 − α)C T ⎛ α ⎞ a K+ = (Kexch)−1⎜ a +⎟ × ⎝1 − α H ⎠ L T − (RT − (1 − α)C T) (2)

where Kexch is the equilibrium constant of the ion-exchange reaction shown in eq 1, α is the deprotonation degree of the chromoionophore, aH+ is the proton activity in the aqueous sample phase, and RT, CT, and LT are the total concentrations of the anionic additive, chromoionophore, and ionophore, respectively. Values of aH+, RT, CT, and LT are known from experimental conditions, and α can be experimentally determined from measured absorbance values, or in the case of paper substrates, approximated from hue values as reported elsewhere:41 H − HP α= HD − HP (3)

Table 1. Obtained Parameters Related to the ISO Reaction solution paper

+

+

log Kexch

log KKexch

log βKL

pKCH a

−1.92a (abs) −2.14b (hue) (log KSol exch) −3.64b (log KCel exch)

−7.85

5.93

−9.65

6.00

7.84 (abs) 8.15 (hue) 8.18

Obtained by curve fitting of absorbance data to eq 2. bObtained by curve fitting of hue data to eq 2. a

In this equation, H represents the hue value at any equilibrium state, whereas HP and HD are the hue values of the fully D

DOI: 10.1021/acsanm.8b00222 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX

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ACS Applied Nano Materials α values and their corresponding Kexch values are used in this work also for the liquid-phase experiments, when directly comparing the response behavior in the liquid phase and on paper substrates, but absorbance-based Kexch values are reported in Table 1, as well. The hue-based response curve for ISO nanoparticles in solution is shown in Figure S4. Despite the use of identical ISO particles, an obvious discrepancy in response behavior between the liquid phase and the paper substrate is observed, as indicated by the significantly differing hue-based Kexch values shown in Table 1. The equilibrium constant for the cation-exchange process of eq 1, Kexch, can be expressed by eq 4:1 + k + a H+[C] [KL+] = K aCH · K ·βKL + · + [CH ] a K [L] k H+

Kexch =

(4)

+

Figure 5. K+-dependent response curves of ionophore-free ISO nanoparticles in the liquid phase and on paper substrates; markers and error bars reflect the average and standard deviations of three ISO particle spots printed onto paper substrates.

where KCH stands for the acidity constant of the protonated a chromoionophore in the organic phase, βKL is the stability constant of the potassium-ionophore (valinomycin) complex in the organic phase, and kK+ and kH+ are the distribution coefficients of uncomplexed K+ and H+ between the aqueous and organic phases. Equation 4 can be rewritten as36,42 +

K Kexch = Kexch ·βKL

(5)

with ⎛ a +[C] ⎞ [K+] + k + K+ Kexch = ⎜ H + ⎟· = K aCH · K ⎝ [CH ] ⎠ a K+ k H+

(6)

+

KKexch represents the equilibrium constant for the ion-exchange reaction in the absence of an ionophore as represented by eq 7. K+ (aq) + CH+ (org) ⇄ K+ (org) + C (org) + H+ (aq) (7)

To investigate the reason for the discrepancy of the Kexch values between the solution phase and the paper substrate experiK+ ments, βKL was evaluated. Kexch can be experimentally determined by fitting the data obtained with ionophore-free ISO particles shown in Figure 5 to eq 8.36 +

K = Kexch

⎛ α ⎞ R − (1 − α)C T ⎜ a +⎟ × T ⎝1 − α H ⎠ a K+

Figure 6. Hue-based pH response curves of ionophore-free nano+

particles used for the determination of pKCH values of CH1 in the a liquid phase and on paper substrates; markers and error bars reflect the average and standard deviations of three ISO particle spots printed onto paper substrates.

(8)

With no significant differences for the solution- and paperbased systems in the ion−ionophore complex stability + constants βKL and the acidity of the chromo-ionophore KCH a , other factors for the discrepancy in overall Kexch values were considered. In contrast to the liquid-phase system (Scheme 1a), additional equilibrium reactions can be considered when working with paper substrates. Cellulosic filter paper is known to have a certain amount of carboxyl groups originating from the oxidation of cellulosic hydroxyl groups during the paper-making process.43 In addition, there are several reports showing that monovalent cations including Na+ and K+ undergo significant interactions with cellulosic carboxyl groups.44−46 Therefore, it can be assumed that in the case of the paper-based system (Scheme 1b), the equilibria according to eqs 9 and (10) cannot be neglected

+

KKexch

With the experimentally obtained Kexch and values shown in Table 1, eq 5 allows to estimate the ion−ionophore stability constant βKL. The values of βKL in the liquid phase and on paper substrates were found to be not significantly different. Since the ion−ionophore complex stability depends on the polarity of the organic membrane phase,22,28 this result indicates the integrity of the plasticized PVC membrane phase of ISO particles applied in the liquid phase and on paper substrates. + KCH was another parameter experimentally determined by a measuring the deprotonation degree of the chromoionophore in ionophore-free ISO particles during exposure to samples of various pH values and fixed ionic strength. For the purpose of direct comparison, the hue-based pH response curves shown in + Figure 6 were used to estimate KCH both in the solution a system and on paper substrates. No significant differences between the two systems were observed. The absorbance signal-based pH response curve for the liquid-phase system is shown in Figure S5.

Cel‐COOH ⇄ Cel‐COO− + H+

(9)

Cel‐COO− + K+ ⇄ Cel‐COOK

(10)

resulting in the overall equilibrium reaction of eq 1 being modified to eq 11: E

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Scheme 1. Schematic Illustration of the Differences between ISO Nanoparticles Applied in (a) the Liquid Phase or (b) on Paper Substratesa

a

In the latter case, the interaction of target cations present in the aqueous solution with carboxylate groups originating from the oxidation of cellulosic hydroxyl groups during the papermaking process must be considered; L: ionophores (valinomycin), C: chromoionophore (CH1), TFPB−: anionic additive (tetrakis-[3,5-bis(trifluoromethyl)phenyl]borate).

ray absorption spectroscopy.48 In the case of the interacting carboxylate group being a formate group, no difference between Na+ or K+ has been noted, while in the case of the carboxylate group being an acetate group, Na+ showed somewhat stronger interaction than K+. In contrast, an example of K+ exhibiting slightly stronger ionic binding affinity to carboxylate anions relative to Na+ has been reported by Tang et al. for a palmitic acid monolayer.46 On the basis of these previous studies, on the one hand, it is concluded that there is little, if any, difference of binding strength between Na+ or K+ ions and carboxylate groups, which depends on the respective nature of the latter. On the other hand, significant differences have been shown for the interaction between Li+ and carboxylate groups compared to other alkali metal ions (Na+/K+).48 This is also supported by the fact that no significant differences in selectivity for K+ over Na+ were observed for the solution phase and the paper substrate systems, whereas response to Li+ is clearly suppressed on paper substrates, as will be discussed later. Although the exact values of pKCel and a pKKCel are unknown, their order of magnitude allows to explain the differences in Kexch values experimentally observed for the solution system and the paper substrate systems by the interaction of the cellulosic paper matrix with the aqueous sample phase according to eq 14. As we reported for the case of ISO membranes applied to filter paper substrates,18 besides being able to bind target analyte cations in the aqueous sample phase, another characteristic of the cellulose matrix potentially influencing the overall ISO response behavior arises from the fact that carboxyl groups on the cellulose surface are capable of behaving as proton source competing with the protonated chromoionophore in the cation exchange process, if contained within the organic ISO phase. However, in contrast to ISO bulk membranes cast onto filter paper substrates, where cellulose fibers are inevitably enclosed into the organic membrane phase, this does not apply to the case of ISO nanoparticles deposited onto a paper substrate, where it can be assumed that cellulose fibers do not form an integral part of the organic ISO phase. This is in agreement with the fact that no differences in the

2K+ (aq) + L (org) + CH+ (org) + R− (org) + Cel‐COOH (aq) ⇄ KL+ (org) + C (org) + 2H+ (aq) + R− (org) + Cel‐COOK (aq)

(11)

Introducing the cellulose acidity constant (KCel a ) according to the equilibrium of eq 9 in analogy to the acid dissociation + constant of the chromoionohore (KCH a ) K aCel =

[Cel‐COO−]· [H+] [Cel‐COOH]

(12)

and the ion association constant according to the equilibrium of eq 10 KKCel =

[Cel‐COOK] [Cel‐COO−]· [K+]

(13)

the equilibrium constant of the ion-exchange reaction shown in eq 11, KCel exch, can in analogy to eq 4 be expressed by eq 14: +

Cel Kexch = K aCH ·

k K+ Sol ·β ·K aCel ·KKCel = Kexch ·K aCel ·KKCel k H+ KL (14)

KSol exch,

where being equal to Kexch defined in eq 4, is newly introduced to unambiguously distinguish between the ionexchange equilibria in the absence and the presence of a cellulosic paper matrix interacting with the aqueous sample phase. On the basis of this equation, the experimentally observed difference of 1.50 (Table 1) between the hue-based ion-exchange equilibrium constants in the solution system in absence of the paper matrix (log KSol exch) and on the paper Cel substrate (log KCel exch) should correspond to the sum of the pKa Cel and pKKCel values. There is no unique report for pKa in the literature. In fact, there exist various values reaching from a pKa of oxidized cellulose of 2.747 up to 4.844 for nanofibrillated cellulose fibrils from wood fibers, and it can be assumed that pK aCel is dependent on the paper substrate used, its manufacturing process, and source of cellulose pulp, among others. Fall et al. have estimated the “association constant” for Na+ ions interacting with cellulose groups on nanofibrillated cellulose fibrils to be in the order of pKNaCel = −2.44 A corresponding value for K+ has not been reported, but it can reasonably be assumed to be of the same order of magnitude.46,48 Uejio et al. experimentally studied the interaction between Na+ or K+ and carboxylate groups by X-

+

acidity of the chromoionophore KCH were observed for the a solution- and paper-based systems. Response Time of ISO Particles on Paper Substrates. Since the cation exchange reaction of ISOs occurs at the interface between the organic ISO phase and the aqueous sample phase, the surface area plays a dominant role in F

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ACS Applied Nano Materials determining the response time. ISO nanoparticles show prominently fast response compared to ISO membranes, owing to their large specific surface area. Typical ISO membranes cast onto solid substrates show response times in the order of several minutes, depending on the membrane thickness and the plasticizer to PVC ratio.49−51 Figure 7 shows

Figure 8. Selectivity evaluation for ISO nanoparticles against lithium ions (Li+), sodium ions (Na+), calcium ions (Ca2+), and magnesium ions (Mg2+): (a) in the liquid phase (based on absorbance data) and (b) on paper substrates. All the samples were prepared in Tris-HCl buffer (pH 7.4, 10 mM); markers and error bars reflect the average and standard deviations of three ISO particle spots printed onto paper substrates.

against various potentially interfering ions in the liquid phase and on the paper substrate. Table 3 summarizes the Table 3. Selectivity Coefficients for Potentially Interfering Ions Figure 7. Time course of the colorimetric response of ISO particlebased PADs upon exposure to 10 mM (○), 1 mM (△), and 100 μM (□) KCl solution. (black dotted line) The hue value of the sensor spot in the as fabricated dry state. (red dotted line) The hue value after the reaction reaches the equilibrium state. (blue line) A 95% hue value change; markers and error bars reflect the average and standard deviations of three ISO particle spots printed onto paper substrates.

liquid phase paper substrate ISO membrane52

Table 2. Comparison of Response Time with Previously Reported ISO-Based Paper Device14 95%

full

≤1 min ≤6 min

≤2 min >10 min

Kopt K+,Ca2+

Kopt K+,Li+

Kopt K+,Mg2+

−3.6 −3.6 −4.0

−5.0 < −5.0 −4.2

−5.2 < −5.2 −4.4

−5.2 < −5.2 −4.4

corresponding selectivity coefficients. In all cases, the experimentally observed selectivity trends are the same as those already reported in the literature for bulk membrane optodes cast on nonporous solid glass substrates.52 However, in the case of Li+, Ca2+, and Mg2+, overall improved selectivity for K+ was observed on paper substrates compared to the liquid phase. This is in agreement with the reported stronger interaction of these cations with carboxyl groups,45,48 resulting in their reduced activities in the aqueous sample phase. Note that there is no significant response of the paper-based system to Li+, Ca2+, and Mg2+ even at high concentrations of these cations (Figure 8b), which prevents the calculation of absolute values for the selectivity coefficients.

the experimental evaluation of the response time of ISO particle-based PADs when exposing as fabricated devices to a 100 μM, 1 mM, and 10 mM KCl solution. Note that the color change occurs almost immediately upon contact with the sample solution (Supporting Video S1). Table 2 shows a

this work previous report (matrix- and plasticizer-free ISO on paper)14

Kopt K+,Na+

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CONCLUSIONS This work successfully demonstrates the highly reproducible fabrication of sub-micrometer-sized inkjet-printable ISO nanoparticles and their application to paper-based colorimetric potassium sensing as an example. Compared to previously reported ISO systems on solid substrates, the nanoparticlebased paper ISOs show significantly faster response times. The unhindered sample liquid wicking over the ISO sensing spots is expected to expand the applicability of paper-based ISOs, for instance, to lateral flow approaches, where a hydrophobic zone within a hydrophilic channel would be detrimental to the overall device performance. Within this work, a comparison of the colorimetric ISO nanoparticle response behavior between the liquid phase and a filter paper platform has been elaborated in detail for the first time. It has been experimentally shown that the presence of a cellulosic paper substrate does have an impact on the behavior of the optode system. However, this impact can be semiquantitatively accounted for by extending the well-known theoretical concept behind cation-exchange optodes, additionally considering the interface between the aqueous sample

qualitative comparison with a previously reported ISO-based PAD,14 demonstrating that the nanoparticle-based system is significantly faster than conventional ISO systems or previously reported paper-based approaches. In fact, the paper-based approach described here is probably among the fastest responding ISO systems using a solid substrate. Another factor contributing to the short response time is the wettability of the ISO-modified paper substrate. In contrast to bulk membrane-coated paper substrates, where cellulose fibers are mostly enclosed into the hydrophobic ISO phase, the use of ISO nanoparticles preserves the liquid wicking properties of the cellulose fibers, resulting in rapid sample transport within the paper layer. Supporting Videos S2a and S2b show the significantly different wicking, wetting, and response behavior of filter paper modified with ISO nanoparticle spots or ISO bulk membrane spots (see Supporting Information for experimental details), respectively. Selectivity on Paper Substrates. Figure 8 shows the result of the selectivity evaluation of the K+-selective optode G

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phase and the cellulosic solid support. We believe that the demonstrated good analytical performance of the current ISO nanoparticle PADs, together with the basic characterization of the ion-exchange reaction mechanism on paper substrates, provides useful insight for further development and application of paper-based ion-selective optode devices.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsanm.8b00222. Fabrication procedure of membrane-type ISO, DLS data of inkjet- and freehand-generated ISO nanoparticles, TEM images of inkjet-generated ISO nanoparticles, absorbance- and hue-based ISO response curves in solution, absorbance- and hue-based pH response curves in solution, description of supporting videos (PDF) Supporting video (AVI) Supporting video (AVI) Supporting video (AVI)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone: +81 45 566 1568. Fax: +81 45 566 1568. ORCID

Daniel Citterio: 0000-0001-7420-045X Author Contributions

The manuscript was written through contribution of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS K.Y. gratefully acknowledges the funding from a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists. The authors thank Prof. E. Bakker of the Dept. of Inorganic and Analytical Chemistry, Univ. of Geneva, for helpful discussion.

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