2508
Anal. Chem. 1992, 64, 2508-2511
Unsymmetrical Calix[ 4larene Ionophore/Silicone Rubber Composite Membranes for High-Performance Sodium Ion-Sensitive Field-Effect Transistors Keiichi Kimura,' Tasushi Matsuba, Y utaka Tsujimura, and Masaaki Yokoyama Chemical Process Engineering, Faculty of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565, J a p a n
As neutral carrlers for sodlum Ion-sensltlve fleld-effect translstors( ISFETs), unsymmetrlcalcallx[4]areneIonophores have been designed whlch possess three ester llnkages and an amlde llnkage as the catlon-blndlng sltes. One of the callx[4]arene derlvatlvesare hlghly soluble In slllcone rubber, whlch Is very adheslve to lnorganlc FET gates, thus affordlng stable senslng membranes for the ISFET. The resultlng sodlum ISFETs based on the callxarene lonophore/slllcone rubber composlte showed hlgh sodlum Ion selectlvlty and hlgh sensor durablllty.
Extensive research has been devoted to designing ionsensitive field-effect transistors (ISFETs) as convenient microscale ion-sensing devices. Nowadays, several inorganic materials are available as stable ion-sensing layers for ISFETs, especially for pH ISFETs. Plasticized poly(viny1 chloride) (PVC) containing active materials are typical organic ionsensing membranes (or layers) for ISFETs as well as ionselective electrodes (ISEs). Although plasticized PVC can afford a variety of ion-sensing membranes by changing the active materials, PVC-type ion-sensing membranes are not very stable as the membranes for ISFETs; they have poor adhesion to the gate surface of the FET, and their active materials and plasticizers are liable to exude from the membranes into the measuring sample solutions. Some effort has, therefore, been made to enhance fixation of the plasticized PVC membranes to F E T gates.',* Room-temperature vulcanizing-type (RTV) silicone rubber may be an excellent alternative to plasticized PVC for organic ion-sensing membranes of ISFETs3 because it possesses high adhesion to F E T gates4and also does not need any additional plasticizer (or solvent) which causes sensor deterioration as seen in plasticized polymer membranes. However, there seems to be some drawback in solubility or dispersibility of ion-sensing material in silicone rubber, which does not contain any special plasticizer (or solvent) unlike plasticized polymers for ion-sensing membranes. This is the case, especially with silicone rubber membranes containing neutral carriers which show high crystallinity. Calix[4]arene derivatives carrying carbonyl linkages a t the lower rim, which are generally Na+ ionophores,5 have proved to be excellent neutral carriers for Na+-selective PVC (1)Harrison, D. J.; Cunningham, L. L.; Li, X.; Teclemariam, A,; Permann, D. J. Electrochem. SOC.1988,135,2473-2478. (2) Moody, G. J.; Thomas, J. D. R.; Slater, J. M. Analyst (London) 1988,113,1703-1707. (3) van der Wal, P. D.; Skowronska-Ptasinska, M.; van den Berg, A.; Bergveld, P.; Sudholter, E. J. R.; Reinhoudt, D. N. Anal. Chim. Acta 1990,231,41-52. (4)Cha, G. S.; Liu, D.; Meyerhoff, M. E.; Cantor, H. C.; Midgley, A. R.; Goldberg, H. D.; Brown, R. B. Anal. Chem. 1991,63, 1666-1672. (5) Arduini, A.; Pochini, A.; Reverberi, S.; Ungaro, R.; Andreetti, G. D.; Ugozzoli, F. Tetrahedron 1986,42, 2089-2100.
membrane electrodes.6~~We have been designing highperformance Na+-ISFETsbased on calix[4] arene ionophores. Most calix[Uarene ionophores are quite soluble in plasticized membranes, but they are not necessarily soluble in silicone rubber. This induced us to design calix[4larene ionophores with a high solubility. Here, we wish to report the high performance of Na+-ISFETs based on silicone rubber membranes incorporating an unsymmetrical calixarene ionophore.
1: R1 = CH2C02C2Hj R2 = C H ~ C O N ( C ~ O H Z I I Z
R2 = C H ~ C O ~ C Z H ~
2:
R1
3:
R1 = C H ~ C G ~ C ~ H S R2 = C H ~ C O N ( C ; H S I ~
4:
R.
=
=
R2 =
CH2C02C2Hj C H ~ C G Z C8H37 ,
EXPERIMENTAL SECTION Synthesis of Unsymmetrical Calix[4]arene Ionophore. Unsymmetrical calixrllarene ionophores 1, 3, and 4 were synthesized by the condensation reaction of tert-butylcalix[4]aryl triethyl ester monoacids with N,N-didecylamine, NJVdiethylamine, and octadecanol, respectively. The typical synthetic procedure is as follows. A mixture of tert-butylcalix[4]aryl triethyl ester monoacid (1.6 mmol) and thionyl chloride (80 mL) was stirred at 50 "C for 3 h. The excess thionyl chloride was then evaporated off to yield the corresponding acid chloride, which was used for a subsequent reaction without further purification. To the acid chloride dissolved in dry benzene (40 mL) was added dropwise with cooling a benzene solution (40 mL) containing triethylamine (1.6 mmol) and an appropriate amine or alcohol (1.6 mmol). The mixture was then refluxed for 3 h. After the reaction, the resulted triethylamine hydrochloride was filtered off. The filtrate was successively washed with dilute HCl and water and was then dried over MgS04. Evaporation of the solvent afforded a crude product of an unsymmetrical calix[4]arene ionophore, which was purified by preparative reversed-phase liquid chromatography (MeOH-CHC13 (70/30)for 1 and 4 and MeOH-CHC13 (9515) for 3 on octadecylsilanized silica). 5,11,I 7,23-Tetra-tert-butyl-25,26,27-tris[ (ethoxycarbonyl)[4]aren41) metho.zyyl-28-[(N~-didecylcarbamoy1)methoxy]calix (yield, 30%): colorless, highly viscous oil (Tp 7 "C); lH NMR (CH&CHs), (400MHz,CDCl3)60.835(~,18H,t-B~),0.874(t,6H,
-
(6) Cadogan, A. M.; Diamond, D.; Smyth, M. R.; Deasy, M.; McKervey, M. A.; Harris, S. J. Analyst (London) 1989,114,1551-1554. (7) Kimura, K.; Miura, T.; Matsuo, M.; Shono, T. Anal. Chem. 1990, 62, 151C-1513. (8) Bohmer, V.; Vogt, W.; Harris, S. J.; Leonard, R. G.; Collins, E. M.; Deasy, M.; McKervey, M. A.; Owens, M. J. Chem. Soc., Perkin Tram. I 1990,431-432.
0003-2700/92/0364-2508$03.00/00 1992 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 64, NO. 21, NOVEMBER 1, 1992
1.2-1.3 (m, 37, H, OCHzCH3 and (CHZ)~CH~), 1.321 and 1.328 (s, 9 H each, t-Bu), 1.5-1.6 (m, 4 H, NCHzCHz), 3.20 and 3.26 (d,
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of high-concentration solutions to the testing solutions while stirring with a magnetic stir bar. Selectivity coefficientsfor Na+ ~ H ~ ~ ~ ~ , A ~ C H Z ) , ~ . ~ - ~ . ~ ( ~ , ~ H , N C H ~ ,with ~ .respect ~ O (to~other , ~ Hcations , O Cwere H Z determined C H B ) , by a mixed solution 4.25 (q, 4 H, OCHZCH~), 4.40 (d, 2 H, OCHzCO), 4.589 ( 8 , 2 H, method (FIM). The background cation concentrations were 1 OCHzCO), 4.60 and 5.08 (d, 2 H each, ArCHz), 4.8-5.05 (m, 4 H, X 10-l M for K+ and H+, 5 X 10-l M for Li+ and Mgz+, 2 x 10-1 OCHzCO), 6.53 (m, 2 H, ArH), 6.633 (s,2 H, ArH), 7.143 (s,4 H, M for CaZ+,and 8 X 10-l M for NH4+. ArH); MS mle (relative intensity) 1243 (M+,65), 57 (100). Anal. Scanning electron microscopy of the ion-sensing membranes Calcd for C78H117N011: C, 75.26; H, 9.47; N, 1.12. Found: C, was conducted at an acceleration voltage of 2 kV. 74.98; H, 9.41; N, 1.11. 5,11,17,23-Tetra-tert-butyl-25,26,27-tris[(ethoxycarbonyl)RESULTS AND DISCUSSION methoxy]-B-[ (NJV-diethylcarbamoyl)methoxy]calix[4]arene (3) (yield, 33%): colorless crystal; mp 157 O C ; lH NMR (400 Design of Unsymmetrical Calix[4]arene Ionophores. MHz, CDC13) S 0.851 (s,18 H, t-Bu), 1.15-1.3 (m, 15 H, CHZCH~), Since many calix[4]arene ionophores are highly selective for 1.310 and 1.317 (8, 9 H each, t-Bu), 3.20 and 3.25 (d, 2 H each, Na+ when complexing alkali and alkaline-earth metal ions, ArCHz), 3.3-3.6 (m, 4 H, NCHz), 4.20 (9,2 H, OCHzCHs), 4.26 they are excellent neutral carriers for Na+-selective elec(q, 4 H, OCHzCHs), 4.41 (d, 2 H, OCHzCO), 4.584 ( ~ , H, 2 OCHztrodes.6~7Most calix[4]arene ionophores incorporating four CO), 4.57 and 5.06 (d, 2 H each, ArCHz), 4.7-5.0 (m, 4 H, OCH2ester or amide linkages, which possess Cdv symmetry, show CO), 6.54 (d, 2 H, ArH), 6.652 (s,2 H, ArH), 7.133 (s,4 H, ArH); high crystallinity and high melting points. Probably due to MS mle (relative intensity) 1020 (M+, 100). Anal. Calcd for the symmetrical structure, which in turn brings about C62H~NOll:c,72.98; H, 8.40;N, 1.37. Found C, 73.05;H, 8.62; comparably high molecular cohesion, the calixf41areneionoN, 1.61. phores are, generally, not very easy to dissolve in polymer 5,11,17,23-Tetra-tert-buty1-25,26,27-tris [ (ethoxycarbonyl)methoxy]-28-[((octadecyloxy)carbonyl)methoxy]calix[4]matrices, sometimes even in plasticized PVC which is often arene (4) (yield, 30%): colorless oil; lH NMR (400 MHz, CDC13) used as a membrane matrix for ISEs. For the purpose of 6 0.834 (e, 18 H, t-Bu), 0.874 (t, 6 H, (CH2)17(CH3),1.2-1.3 (m, fabricating stable ion-sensing membranes for Na+-ISFETs, 41 H, OCHzCH3 and (CHz)&H3), 1.326 and 1.337 (s,9 H each, cross-linked polysiloxane, otherwise called silicone rubber, t-Bu), 3.21 and 3.27 (d, 2 H each, ArCHz),4.1-4.3 (m, 8 H, ( 2 0 2 which has good adhesion to FET gates and does not need any CH2), 4.38 (d, 2 H, OCHzCO), 4.596 ( ~ , H, 2 OCH&O), 4.61 and plasticizer, was employed in this study. Solubility of calix5.05 (d, 2 H, ArCHz), 4.85-5.0 (m, 4 H, OCHzCO), 6.550 (8, 2 H, [Ilarene ionophores is more crucial in silicone rubber ArH), 6.655 ( 8 , 2 H, ArH), 7.152 and 7.162 ( 8 , 2 H each, ArH); membranes than in plasticized PVC membranes, because the MS mle (relative intensity) 1217 (M+,2.4), 57 (100). Anal. Calcd former membranes do not include any special plasticizer in for C76H11~N012:C, 74.96; H, 9.27. Found C, 74.46; H, 9.45. which the ionophores may be soluble. In order to improve Other Materials. tert-Butylcalix[4]aryl tetraethyl ester 2 was prepared according to a procedure in the l i t e r a t ~ r e .Unless ~ the solubility of calix[4]arene ionophores in silicone rubber, otherwise noted, the one-component RTV silicone rubber emwe have designed an unsymmetrical calix[41arene ionophore ployed was Shin-Etsu Silicone KE44T, where cross-linking and which possesses three ethyl ester linkages and an amide thereby hardening of the polysiloxane was achieved by oximelinkage with longer alkyl chains at the phenoxy positions, 1. evolving condensationof its silanol and a ketoxime-silane. Similar As compared with a symmetricalcalix[4]arene ionophore such alcohol-type(KE47T) and acetone-type (KE3479T)RTV silicone as 2, the unsymmetrical one possesses only low symmetry, rubbers were also used. Poly(viny1 chloride) (PVC) with an i.e., C, symmetry, thus being quite amorphous. Two other average polymerization degree of 1100 was purified by recalix[Uarene ionophores with different unsymmetrical moiprecipitation from THF in methanol. 2-Ethylhexyl sebacate eties were also synthesized for comparison with l. One of (DOS) was purified by vacuum distillation. Benzene and tetrahydrofuran (THF) were distilled over Na. Chloroform was them, 3, contains a n amide carbonyl linkage but no long simply distilled before use. Alkali and alkaline-earth metal aliphatic chain. Although 3 possesses a high melting point, chlorides and ammonium chloride were of analytical reagent it also turns out to be an amorphous glass by melting, followed grade. by cooling to room temperature. The other, 4, carries a ISFET Fabrication. ISFET tips, which were kindly supplied dodecyl group as the long aliphatic chain and an ester carbonyl by Shindengen Electric, possess a gate size of 10 X 370 pm, as linkage instead of the amide one, possessing unsymmetry previously described.lO An aliquot (2 pL) of a chloroform (or only in the aliphatic chain. All of the unsymmetrical tetrahydrofuran) solution (300pL) containing a mixture (50 mg) calixarene ionophores possess a "cone" conformation, which of calixarene ionophore and RTV silicone rubber was placed on is preferable to the three other conformations for Na+ the gate surface of an ISFET tip, using a microsyringe. The complexation, as evidenced by two pairs of doublets for the ISFET tip was allowed to stand at ambient temperature for 2 days for solvent evaporation and hardening of the ion-sensing aromatic-ring-bridging methylenes in the 'H-NMR spectra. membrane. Typically, the chloroform solution of 5 mg of ISFET Response. The unsymmetrical calix[4]arene ionophore and 45 mg of siliconerubber afforded membranes with ionophore, 1,was applied first to Na+-ISFETs based on DOS10w t % calixareneionophorecontent and about 100-pmthickness plasticized PVC. A typical symmetrical calix[4larene ionafter the hardening. Controlling the membrane thickness was ophore, 2, was employed as well for comparison. The resulted achieved by varying the concentrations of ionophore and silicone Na+-ISFET based on a PVC/DOS/l membrane exhibited a rubber in the chloroform. PVC membranes were prepared by Nernstian response (59 mV decade-') to Na+ activity changes dipping an ISFET tip in a solution consisting of PVC (15 mg), in the range of 1 X 10-4 to 1 M as is the case with the DOS (30 mg), calixarene ionophore (5 mg), and tetrahydrofuran corresponding 2 membrane. The ISFET based on plasticized (300 pL) several times. The resulted ISFETs were conditioned M NaCl aqueous solution. The ISFETs, by soaking in 1 X PVC of 1 also possesses high Na+ selectivity against other when not in use, were usually also kept in the NaCl solution. alkali and alkaline-earth metal ions, which is similar to that Measurements. Potential measurements were made at room for the corresponding 2-based ISFET, as will be described temperature using an ISFET pH/mV meter (Shindengen Eleclater. Also, the other unsymmetrical calixarene ionophores, tric). The source-drain voltage ( V b ) and current (Zb) were 3and 4, when employed as neutral carriers for DOS-plasticized adjusted to 5 V and 100 (or 150)MA,respectively. The reference PVC membranes, exhibited similar ISFET responses to 1 electrode was a double-junction type Ag/ AgCl electrode with 3 and 2. M KC1 internal solution and 1M CH3COzLi external solution. For improvement of ISFET durability, a one-component The measuring cation concentrations were changed by injection RTV silicone rubber of the oxime-evolvingtype was attempted (9) Chang, S.-K.;Cho, I. J. Chem. Soc.,Perkin Tram. 1 1986,211-214. as the membrane matrix. Figure 1shows a typical potential (10) Kimura, K.; Mataute, M.; Yokoyama, M. Anal. Chim. Acta 1991, response of a Na+-ISFET based on a silicone rubber mem252,41-46.
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ANALYTICAL CHEMISTRY, VOL. 64, NO. 21, NOVEMBER 1, 1992
I
A
59mV decade
'
45
/
40
* Od 5
4
3
2
1
0
-log [Na']
Flgure 1. Potentlal responseto Na+ activity changes of ISFETs based on silicone rubber membranes of callxarene ionophores. callxarene Ionophore: 1 (0),2 (01,3 (O), 4 (A).
brane containing 10 wt % unsymmetrical calix[4]arene ionophore 1. A Nernstian response to Na+ activity changes was attained in the range of 1 X to 1M with the silicone rubber/ 1membrane. The potential response is very fast, the response time being within 2 s for a 10-fold Na+-activity increase. It should, however, be noted that a similar silicone rubber membrane of symmetrical calixr4larene ionophore 2, when applied for Na+-ISFETs, exhibits a poor response to Na+activity changes. The silicone rubber membrane of 2 is very different in the ISFET response from the corresponding PVC membrane. This poor response of the silicone rubber membrane of 2 is derived mainly from low solubility of 2 in silicone rubber. Scanning electron microscopy gave some information about the solubility of 2 in silicone rubber. Microcrystals of 2, which were not very compatible with silicone rubber, were observed on the silicone rubber membrane of 2, while the corresponding 1 membrane possesses a smooth surface, implying good compatibility of the unsymmetrical calix[4]arene ionophore with silicone rubber. Calixarene ionophore 3 is also quite soluble in silicone rubber. In Na+-ISFETs with 3/silicone rubber membranes, a Nernstian response was found in the range of 1 X to 1X 10-1 M Na+,but the sensitivity was decreased more or less at higher Na+ activities. On the contrary, calixarene ionophore 4, although also unsymmetrical, bears only poor solubility in the polymer matrix. Serious phase separation was observed in the lisilicone rubber membranes, thus resulting in poor ISFET sensitivity. The high solubility of 1in silicone rubber and therefore high ISFET sensitivity are based mainly on the unsymmetrization of calixarene ionophores by the incorporation of an amide carbonylgroup.There also seems to be some contribution of the unsymmetrization by adopting a long aliphatic chain to the solubility enhancement. Two other RTV silicone rubbers of alcohol- and acetoneevolving types were also tested for their usefulness as a membrane matrix for the calixarene-based Na+-ISFETs. Very similar ISFET properties to those for the silicone rubber of the oxime-exolving type were found in the 1-based Na+ISFETs using the two other silicone rubbers. We decided to use the oxime-evolving type silicone rubber throughout this study, due to its wide use and quick hardening. Membrane Optimization. Attempts were made to optimize the ionophore content and membrane thickness in the silicone rubber/ 1 membrane system. Sensitivity and selectivity were followed in the Na+-ISFETs based on several silicone rubber membranes with different contents of calixarene ionophore 1. The optimal ISFET sensitivity requires calixarene contents of more than 5 wt %, the silicone
15
10
20
Calixarene Content wt%
I 6
~
5
Figure 2. Seiectivltydependence on callxareneIonophore content for Na+-ISFETs based on sillcone rubber/l membranes. 70 -
:
40
t/
i:y
6oo;
,
10 OO
100
200
M e m b r a n e Thickness
i pm
Flgure 3. Sensitivity dependence on thlckness of ion-sensing membranes In Na+-ISFET based on sillcone rubberll membranes.
membranes of which exhibit Nernstian response up to 1 M Na+ concentration in the presence of a 0.1 M K+ background. For the membranes having a lower calixarene content, the sensitivity was decreased, especially in the high Na+ concentration range. The selectivity coefficient for Na+ with respect to K+ in the Na+-ISFETs based on silicone rubber/l membrane was decreased with an increase in the calixarene content, as demonstrated in Figure 2. Above 7 w t % calixarene content, the selectivity coefficient leveled off at about 3 X Thus, a calixarene content of 10 wt % for the Na+ISFETs based on silicone rubberil membranes is quite reasonable from the standpoint of the sensitivity and ion selectivity. Figure 3 is concerned with the optimization of ion-sensing membrane thickness for Na+-ISFETs based on silicone rubbed1 membranes. Slopes for the Na+ calibration graph (potential changes a t 10-fold Na+ activity changes), i.e., the ISFET sensitivities, were followed based on the membrane thickness. Only poor sensitivity was found in the Na+-ISFET with a very thin ion-sensing membrane (about 10 pm). Increasing membrane thickness raised the ISFET sensitivity, and above 70-pm thickness, the slope leveled off a t 59 mV decade-l, which corresponds to the Nernstian response of Na+-ISFETs. Very thin membranes, although desirable for rapid ISFET response, did not realize sufficient sensitivity. Membrane thickness of about 100 pm is, therefore, required for the Nernstian response of the Na+-ISFETs based on silicone rubber/ 1 membranes. Selectivity Comparison. Ion selectivities for the Na+ISFETs based on the optimized silicone rubber/l membranes are summarized in Figure 4, together with those for the ISFETs based on plasticized PVC membranes of 1 and 2 for comparison. The selectivity coefficient for Na+ with respect to K+, which is an important factor for practical use of Na+ sensors, for the silicone rubbed1 system is equivalent or even superior to the plasticized PVC/l and 2 systems, being 3 x Incorporation of additional anionic sites as a lipophilic
ANALYTICAL CHEMISTRY, VOL. 04, NO. 21, NOVEMBER 1, 1992
Na'
-1 O I
-
Na'
2511
- Na'
-
30;
20
40
60
80
100
I20
Period I day Silicone R u b e r i l
PVCiOOSil
PVC+DOS+Z
( 90110 wl% ) ( 30160110 wt% j ( 30160110 Wt% )
Fburr 4. SelectMtycomparison among calixarene-based Na+-ISFETs.
salt [such as potassium tetrakis@-chloropheny1)boratel to the silicone rubber/ 1 membrane might enhance the ISFET performance more or less.11 Durability Test. Time-course changes in both sensitivity (slope for Na+ calibration graph) and selectivity (selectivity coefficient for Na+ with respect to K+) were followed in the Na+-ISFETs based on ion-sensing membranes of silicone rubber/l, PVC/DOS/l, and PVCIDOSI2 (Figures 5 and 6). Deterioration proceeded quite quickly in the Na+-ISFETs of PVCIDOSIB; in about 30 days, both the Na+ sensitivity and selectivity were drastically decreased. This occurred because the plasticizer and neutral carrier 2 dissolved out from the membrane into the aqueous phases. In the Na+-ISFETs of PVC/DOS/ 1 membranes, marked deterioration started a t about 50 days, i.e., muchmore gradually than the PVC/DOS/2 system. This implies that the unsymmetrical calix[Uarene 1is very superior to the symmetrical one 2 in solubility even in PVC. Nevertheless, leaching of the plasticizer out from the PVC/DOS/l membrane led to such ISFET deterioration. On the other hand, attention should be drawn to the excellent durability of the Na+-ISFETs containing silicone rubber/ 1 membranes. In these ISFETs, their high Na+ sensitivity and selectivity remained unchanged even after 120 days. In conclusion, the composite membranes of unsymmetrical calix[Uarene ionophore 1 and RTV silicone rubbers have (11)Huser, M.; Gehrig, P. M.; Morf, W. E.; Simon, W.; Lindner, E.; Jeney, J.; Toth, K.; Pungor, E. Anal. Chem. 1991,63,1380-1386.
Flgwo 5. Tlme-cowse changes of sendtlvky for calkarene-based Na+-ISFETs. silicone rubber11 (90110 wt %) membrane (0),PVCI DOSll (30/00110 wt %) membrane (01,PVCIDOSl2 (30/00110 wt %) membrane (A).
*O
20
40
60
80
100
12(
Period / day Flgwr 6. Tlme-course changes of selecttvlty for callxarene-based Na+-ISFETs. The symbols are ldentlcal wlth those In Figure 5.
realized long-lived Na+-ISFETs possessing excellent Na+ selectivity and sensitivity.
ACKNOWLEDGMENT Thanks are due to the Instrumental Analysis Center, Faculty of Engineering, Osaka University, for assistance in obtaining NMR (JEOL JNM-GSX-400) and mass (JEOL JMS-DX303) spectra. The present work was partially supported by a Granbin-Aid for Scientific Research No. 04650681 from the Ministry of Education, Science, and Culture. RECEIVEDfor review March 30, 1992. Accepted July 27,
1992.
