Sensors and Actuators B, 15-16 (1993) 81-85 81

Bilayer membrane for ISFETs to eliminate CO2 mediated pH sensitivity

John Shaw THORN EM CRL, Dawley Road, Hayes, Middx. UB3 IHH (UK)

Abstract

The basis of neutral species mediated pH interference for polymer membrane ISFETs and strategies for eliminating this interference are discussed. The use of an alkali sensitive glass layer between gate insulator and polymer is proposed, and experimental results presented for such structures.

Introduction

Use of polymeric membranes, especially plasticised PVC with ionophores, on ISFETs is well established as a means of providing sensitivity and selectivity to a wide range of cations and anions. The gate insulators normally used in ISFET fabrication, SiO, and S&N,, when exposed to aqueous solutions undergo surface ion exchange processes, especially involving H+. As a result bare gate ISFETs show clear pH sensitivity, though often with significant drift and interference from alkali metal cations. Effective gate voltage for a membrane coated ISFET includes contributions from the solution/ membrane interface, and the membrane/insulator inter- face. A polymer membrane composition, e.g. ionophore choice and content, is directed towards establishing a membrane/solution interfacial potential selectively sen- sitive to the target ion, and for good selectivity for the device it is a necessary requirement that all other inter- facial potentials (indicated diagrammatically in Fig. 1) remain constant.

interest. Alternatively, specific effects at the insulator/ polymer interface may not have been identified due to the variety of possible causes of unstructured drift.

Polymeric membranes with ionophores whilst ex- hibiting selectivity between ions, remain generally per- meable to neutral species which can include HPOvap, CO*, Oz, and organic molecules including unionised weak acids and bases. The relatively permeable nature of polymeric membranes to neutral species provides a means by which the nature of the insulator/polymer junction, and hence the interfacial potential profile, may be modified by, and respond to, the solution composition. The insulators used provide a hydrophilic surface at which water may be expected to accumulate, though possibly only as a fragmented molecular layer. The acid/base reaction of some neutral species, in combination with the pH sensitivity of the insulator surfaces, provides the most obvious mechanism by which the insulator/polymer interfacial potential may be altered.

In retrospect it appears surprising that it was not until 1985 that clear ‘evidence was presented in the literature [l] for chemical response modification linked to changes at the insulator/polymeric membrane inter- face. Certainly the problem of defining the character and interfacial potential at this type of junction had been under consideration for some years earlier [2]. The insulator/polymer membrane interface should not be regarded as blocked, as both surfaces are clearly capa- ble of ion exchange. In such a conductive environment charge trapping at the interface cannot be the basis for shifts in characteristics. The fact that polymer mem- brane ISFETs were in very many investigations found to give satisfactory selectivities, indicated that if there was a problem with the insulator/polymer interface, it was often not of a serious nature, or substantial only for ranges of solution composition not normally of

Cross sensitivity to pH mediated by CO, transfer through PVC membranes was first reported by Fogt et al. [ 11. It is clear that this type of process can seriously interfere with the selectivity of polymer mem- brane ISFETs, especially for biological samples which commonly contain molecules with the potential to cross polymeric membranes. While the direction of shifts in effective gate bias is readily understood on the basis of transport of acid or base reacting species across the membrane, their values are less predictable.

Interferences of the type described should not be possible where the insulator is overlain by a membrane impervious to neutral species. While the permeability to molecular species of many inorganic membranes will be very low, their use alone is very restrictive in terms of selectivity. Various strategies have been suggested aimed at overcoming the effects of neutral species per- meability of polymeric membranes, and these most

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82

V REF

ELECTROLYTE

SOLUTION

I

OHWlC N CONTACT 5

U P 1

Si A f 0 R

ION RESPONSIVE

INTERFACE

Fig. 1. Diagrammatic representation of potential profiles for an ISFET with membrane

generally involve the addition of a further layer between insulator and polymer.

The use of a metal layer between polymer and gate insulator has been proposed [3], but is unsatisfactory due to combinations of O2 partial pressure and pH sensitivity at metals and metal oxide layers.

Use of an aqueous buffered layer between ISFET insulator and polymeric membrane has been described [4]. This approach involves penalties, both in terms of fabrication and operation. Small size is a major basis for the use of ISFETs rather than ISE devices, but this must inevitably limit the butler capacity of any layer. Ensuring cast polymeric membranes covering aqueous buffer layers do not leak and are not ruptured by osmotic pressure effects, provides a formidable chal- lenge.

Suppression of pH response at an insulator surface by blocking exchange sites has been proposed and to a limited extent demonstrated [5]. A blocked interface below a conventional polymeric membrane would re- duce neutral species mediated pH interference. However ionisable species, migrating in their uncharged form to the interface, may bind there and progressively unblock the interface, with consequent drift in the interfacial potential and device characteristics. Where the surface

below the polymer membrane has very many effective exchange sites, as for the conventional insulators or the layers described below, the effect of further ionisable species binding to the surface is minimised.

The successful use of a layer of Ag/AgCl or simply AgCl to suppress the neutral species mediated pH inter- ference effect on ISFETs has been described [6,7]. Those papers confirm that the effect can arise through migration of weak organic acids, such as benzoic acid, as well as CO,. While the pH at the AgCl/polymer membrane surface may change, the AgCl layer effec- tively screens that layer from the pH responsive insula- tor, and maintains a stable junction by Cl- or Ag+ exchange. The use of AgCl as an interlayer is estab- lished in solid state ISE devices [8].

Compositions exist in aluminosilicate and borosili- cate glass systems which yield membranes primarily sensitive to alkali metal cations [9] and show relatively low sensitivity to Ht. Such inorganic glasses will in addition to their ionic permselectivity also show low permeability to neutral species. Unfortunately, except- ing compositions selectively responsive to H+, and oth- ers selective to Na+, the available glasses are quite unable to match the ion selectivities achievable by the wide range of ionophore/polymer combinations. Means

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of depositing and photolithographically defining glass layers on ISFET devices have been established, primar- ily to produce devices with pH and pNa membranes formed at the wafer fabrication stage. The glass layers are adherent and reasonably robust. On the basis de- scribed above, an alkali ion responsive glass interlayer should establish a stable interface by alkali ion ex- change and suppress neutral species mediated pH inter- ference.

Experimental

The experimental work involved production and chemical response testing of ISFETs with cast polymer membranes (K+ responsive plasticised PVC/valino- mycin). Membrane arrangements examined included cast polymer directly over S&N, gate insulator, and cast polymer over sputtered Ta,05 (pH responsive) and aluminosilicate glass (Nat responsive).

Inorganic membranes (glasses, Ta,O,) were formed on ISFET devices by sputter deposition and patterning. Dual gate ISFETs (CRL600/601) with sputtered mem- branes have been subjected to tests of response to pH and alkali cation concentration change and results as shown in Fig. 2 confirm that the altinosilicate glass composition used showed near Nemstian response to alkali cations and very low sensitivity to pH.

Tests on pH sensitivity of plasticised PVC/valino- mycin membrane ISFETs in bicarbonate/CO, were car- ried out using dual gate ISFETs where the polymer membrane cast from THF/cyclohexanone solution

, I

T I Glass T=Jk

d- - 1 . l-----m B ABA CB D E D

e 5 10 15

tir (rin)

Fig. 2. Response of aluminosihcate glass and Ta,Os membrane ISFETs to pH and sodium ion concentration changes.

Solutions Nat (mM) K+ (mM) PH

6n MOLAR KC1

I \

10 nv

6n MOLAR

KC! PVC MHBRANE

ON Gm/Si3NG

PVC HEHBRAWE

ON Si,N,

0

I 10 PIINS 4

Fig. 3. Potassium ion concentration response of ISFETs with PVC/valinomycin membrane overyling S&N, and aluminosilicate glass gates.

overlaid one bare Si,N, gate and one gate sputter coated with the alkali ion sensitive glass. Devices were cycled between solutions made up to 110 mM NaCl, 25 mM NaHCO,, with 3 or 6 mM KCI, and adjusted to pH 8.1 or 6.9. Results obtained are shown in Figs. 3 and 4. Both gates showed similar sensitivity to changes in K+ concentration ( - 18 mV). The response of S&N,/ glass/PVC gates to pH changes was very small, while that for Si,NJPVC gates was substantial (> 10 mV over two minutes), reversing when the pH change is reversed. This pH response was much slower than that to K+ as is consistent with a process requiring diffusion of CO, through the polymer. The non-pa responsive, gas impermeable glass layer maintains a series of stable junction potentials.

ISFET devices with PVC/valinomycin membranes cast over gates with sputtered Ta,05 and aluminosili- cate glass layers have been tested for response to potas- sium ion concentration, and for pH interference in

I -$--k ,CtH;HBRANE

1OnV pH81 1 pH 6.9 1 pH61

PVC IIEIWRANE

ON w ON Si,N,

A 300 7.56 B 140 1.45 C 70 7.56 D 150 10 6.98 E 150 10 7.57

0

I 10 WNS. -1

Fig. 4. Response to pH of bicarbonate solutions for ISFETs with PVC/valinomycin membrane overlying S&N, and ahuninosilicate glass.

84

G1a.w grte I PVC -Val.

10.8 6.8 pH

1 min. u i

Fig. 5. Response to pH of bicarbonate solutions for ISFETs with PVC/valinomycin membrane overlying Ta,O, and aluminosilicate glass. Carbonate buffered solution: 0.1 M KCI, 0.025 M Na,CO,

solutions containing bicarbonate or acetate. Response to potassium in phosphate of ‘Tris’ buffered solutions, where pH changes were very limited, was as expected near Nemstian irrespective of the sputtered layers. Fig- ure 5 shows response to change in pH at fixed K+ for solutions containing bicarbonate. While the glass inter- layer effectively suppressed any significant pH effect, the Ta20, interlayer gate showed a response which was much more significant for neutral to alkaline, than for acid pH values. As indicated in Fig. 6, similar pH effects were discernible in the presence of acetate buffer. Although the effect may be mediated by the diffusion of unionised acetic acid through the PVC membrane, the pH values for maximum effect did not appear to corre- late with the p& for acetic acid (4.76).

It is clear from Fig. 4 that response of the Ta,O,/ polymer gate to solution pH changes is hardly dis- cernible for pH < 6, and is probably concentrated around pH 8. Trial calculations indicate that the basis of this behaviour may lie in the effective concentration and pK, of weak acids or exchange sites at the polymer/ Ta,O, interface. It might alternatively or additionally reflect some partial blocking of exchange sites which may reduce and restrict pH sensitivity [S].

During the experiments, it was generally observed that, even when direct pH response was unclear, PVC membrane devices showed enhanced drift in bicarbon-

ate or acetate solutions as compared to phosphate buffered solutions. This suggests the existence of pro- cesses slower than direct pH response following media- tor diffusion. This may reflect changes in blocking of electroactive sites at the insulator surface.

Alkali ion selective glasses can be sputter deposited on ISFET devices, and when directly contacting solu- tion show low pH response. When such glasses are used as an interlayer between insulator and polymer mem- brane, the ISFETs produced are essentially immune to neutral carrier mediated pH response.

The neutral carrier mediated pH response for Si,N, or Ta,O, gates below PVC membranes appears to be at a very low level except over a restricted pH range. This may be compatible with a limited buffer capacity, possi- bly with pK, around 8.

The time scale for the neutral species mediated pH effect on polymeric membrane ISFETs should depend on the diffusion times for those species. Expressions for diffusion across plane sheets [IO] with membrane thick- ness of lOGlO pm and diffusion coefficients of 10M6- 10m9 cm2 s-’ predict times to 80% completion of total flux in the range I- 1000 s. The response times observed

pH 1.9 4.8 12.7 2.2 3.7 4.8 4.8 6.0 7.9 6.0 4.8 3.7 2.2

Fig. 6. Response to pH of acetate solutions for ISFET with PVC/valinomycin membrane overlying Ta,O,. Acetate buffered solution: 0.5 M KCI, 0. I M NaCH,CO,.

are compatible with diffusion coefficients in the region of 10-7 cm2 SK’.

Devices fabricated using bilayer membranes of the type described in this paper have been used in studies on whole blood showing good correlation between ISFET and ISE based equipment [ 111.

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