Abstract
The aim of this work concerns the transduction of chemical information, given by molecular receptors, into electric signal by field effect transistors (FETs). Field effect transistors are attractive transducing elements because they are able to register and amplify chemical informations at the gate oxide surface of the semiconductor chip. For this reasons they could be applied as transducers in electrochemical sensors, that can communicate changes of substrate activities in aqueous solutions (ISFETs, CHEMFETs) or maintain a stable potential in different ion activities (REFETs). Several results of studies, carried out by our group, concerning the application of FETs in ion potentiometric sensors and reference sensor were presented.
Introduction
Chemical sensors represent microdevices that connect the chemical and electrical domains (i.e. transduction of the chemical information into electronic signal). The response of sensors on changing activities of chemical molecules in aqueous solutions should be fast and selective for one species. Moreover, these devices should have a lifetime in the order of months. The construction of chemical sensors requires the integration of a sensing receptor and a transducing element into a defined chemical system. As the transducing element field effect transistors (FETs) are very interesting because they can made very small with available planar IC technology and have the advantage of a fast response time.
This paper describes the present state of art in the application of field effect transistors as transducers in electrochemical sensors. Firstly, the characterisation of metal oxide semiconductor field effect transistor (MOSFET), measurement system and the sensing properties of gate surface of ion-sensitive field effect transistor (ISFET) were reported. Secondly, the development of different potentiometric cationic and anionic sensors based on chemically modified ISFETs (CHEMFETs) were presented. Finally, we showed our studies and our contribution in the development of chemical modified FETs and in development of the reference field effect transistor (REFET).
From MOSFET to ISFET
The field effect transistors are able to measure the conductance of a semiconductor as a function of an electrical field perpendicular to the gate oxide surface. In the most simple well-known form, a metal oxide semiconductor field effect transistor (n-channel MOSFET), a p-type silicon substrate (bulk) contains two n-type diffusion regions (source and drain). The structure is covered by a silicon dioxide insulating layer on top of which a metal gate electrode is deposited (figure 1a).
When a positive voltage (with respect to the silicon) is applied to the gate electrode, electrons (which are the minority carriers in the substrate) are attracted to the surface of the semiconductor. Consequently, a conducting channel is created between the source and the drain, near the silicon dioxide interface. The conductivity of this channel can be modulated by adjusting the strength of electrical field between the gate electrode and the silicon, perpendicular to the substrate surface. At the same time a voltage can be applied between the drain and the source (Vds), which results in a drain current (Id) between the n-regions.
In the case of the ISFET (ion-sensitive field effect transistor) the gate metal electrode of the MOSFET is replaced by an electrolyte solution which is contacted by reference electrode (then the SiO2 gate oxide is placed directly in an aqueous electrolyte solution (figure 1b) [1].
Figure 1. Schematic representation of a MOSFET (a), and a ISFET structure (b).
The metal part of reference electrode can be considered as the gate of the MOSFET.
In ISFET electric current (Id) flows from the source to the drain via the channel. Like in MOSFET the channel resistance depends on the electric field perpendicular to the direction of the current and thus on the potential difference over the gate oxide. Since, the source-drain current Id is influenced by the interface potential at the oxide/aqueous solution. Although the electric resistance of the channel provides a measure for the gate oxide potential, the direct measurement of this resistance gives no indication of the absolute value of this potential. However at a fixed source-drain potential (Vds), changes in the gate potential can be compensated by modulation of the Vgs. This adjustment should be carried out in such a way that the changes in Vgs applied to the reference electrode are exactly opposite to the changes in the gate oxide potential. This is automatically performed by an ISFET amplifier due to feedback; the source-drain current is kept constant. In this particular case the gate-source potential, being the output potential of the amplifier, is determined by the surface potential at the insulator/electrolyte interface.
When SiO2 was used as insulator, the chemical nature of the interface oxide is reflected in the measured source-drain current. The surface of the gate oxide contains OH-functionalities, which are in electrochemical equilibrium with ions in the sample solutions (H+ and OH-). These hydroxyl groups at the gate oxide surface can be protonated and deprotonated and thus when the gate oxide contacts an aqueous solution a change of pH will change the SiO2 surface potential. A site-dissociation model describes the signal transduction, as a function of the state of ionization of the amphoteric surface SiOH groups [2,3]. Typical pH responses measured with SiO2 ISFETs are 37-40 mV/ pH unit [3].
Since, the selectivity and chemical sensitivity of the ISFET are completely controlled by the properties of the electrolyte/insulator interface. It has been shown, that other inorganic gate materials for pH sensors like Al2O3, Si3N4 and Ta2O5 have better properties in relation with pH response, hysteresis and drift than SiO2. In practice, these layers are simply deposited on top of the first layer of SiO2 by means of chemical vapour deposition (CVD).
The choice for an ISFET as a transducing element was based on the fact, that the SiO2 surface contains reactive SiOH groups for the covalent attachment of organic molecules and polymers. In addition the FET has fast response times and can be made very small with existing planar IC technology.
MEMFET and SURFET
When the presented ISFET is modified with a sensing membrane, that contains an ionophore, the membrane potential determines the response of the sensor [4]. If the gate oxide is covered directly by an ion-sensitive membrane, the device is known as a MEMFET [5]. In this case the ion-sensing layer is penetrable for ions (unblocked); the membrane potential is generated throughout the membrane, and is detected by the FET structure. The first ISFET modified with a sensing membrane containing an ionophore, which enables the detection of the activity of an ion by his complexation, was reported by Moss [6]. A K+-sensitive FET was obtained by solvent casting of a conventional plasticized PVC membrane, containing valinomycin on the gate oxide surface. Other approaches proposed Ca2+ sensitive MEMFET (with ion exchanger in polymeric membrane) [7] or deposition of AgBr membranes (Ag+ or Br- sensors) [8].
SURFET represents an ISFET with an ion-blocking layer, which covers the pH-sensitive sites of the gate insulator. At the surface of this layer a surface potential is established by selective association of ions. An example of a SURFET is the parylene gate ISFET with attached benzo-18-crown-6 ionophore molecules, that selectively complex potassium ions [9]. In opposition to the MEMFET, where the association coefficient of the ionophore with recognised ion in the membrane phase determines the selectivity, in SURFET the same quantity in the aqueous phase controls the selectivity. Since the latter is usually much smaller and we focused our attention on the MEMFET type sensors.
From the literature reviev [10,11], it can be concluded that MEMFETs are readily fabricated by means of solvent casting of PVC membranes, with incorporated plasicizer and ionophore, on top of the ISFET gate oxide. Such simple systems, based on the physical attachment, have the disadvantage that the membrane releases easily from the surface (poor adhesion of the membrane to the gate oxide) so that membrane electroactive components may leach out. The latter effect can be removed by using extremely hydrophobic receptor or the ionophore can be covalently linked to the organic matrix at the ISFET gate oxide [12]. However, there is no thermodynamically well-defined membrane-ISFET interface and finally the pH sensitivity is not completely eliminated.
CHEMFET
As mentioned ISFEts modified with plasticized PVC membranes lack a thermodynamically well-defined interface between the sensing membrane and the solid contact. Despite this, the PVC-modified ISFETs do not seem suffer from the ill-defined inner contact and acceptable stabilities and drift values have been reported [7, 13,14]. This apparently satisfactory behaviour of these devices was the main reason why no experimental efforts were made to improve this system. However following studies showed, that changes of carbon dioxide concentrations in the sample solution interfere strongly with the measurements [15]. This was attributed to the diffusion of carbon dioxide through the membrane and the successive formation of carbonic acid at the membrane-gate oxide interface with traces of water present at the interface. Consequently, the concentration of protons, which are the potential determining ions at the membrane insulator interface, undergo large variations depending upon the CO2 concentration. This would also explains why ISFETs modified with PVC membranes generally perform satisfactory (the PVC membranes usually contain reasonable amounts of water and therefore H+ ions will be present as well and control the membrane-insulator potential). Besides the above mentioned CO2 interference, the need for high amounts of water inside the membrane matrix was the final argument that urged to develop a thermodynamically well-defined interface.
As possible solutions for these problems, several approaches have been described in the literature for FET based sensors. In most cases, an intermediate Ag/AgCl layer is applied on the gate-insulator surface [16], which at least eliminates the CO2 interference. Various methods to deposit the Ag/AgCl layer on a silicon substrate were reported with conclusion, that different IC-compatible methods give satisfactory layers [17]. However, the Ag/AgCl-membrane interface becomes critical. The equilibrium state of this interface relies on the exchange of scarcely present Cl- ions in the membrane. Therefore, a better approach seems to place an additional layer like sodium glass between the polymer and the gate insulator or poly(vinyl alcohol) between the polymer and an Ag/AgCl layer on top of the gate insulator [18]. In this, way common ions can be provided by the intermediate layer.
Another approach, a novel architecture - chemically modified FET (CHEMFET), is designed to solve the problems mentioned above (figure 2).
Figure 2. Schematic representation of a chemically-modified field effect transistor - CHEMFET. Top: cross-section through the various layers with potential determining species
The attachment of the membrane can be improved by mechanical [19] or chemical [20,21] anchoring to the surface of the gate oxide. For chemical attachment of polymer films the gate oxide surface is first silylated with 3-(trimethoxysilyl)propyl methacrylate. The methacrylate modified surface can subsequently react with vinyl or methacryl monomers or prepolymers. The use of UV-photopolymerizable monomers, hydroxyethyl methacrylate (HEMA), is advantageous in view of the ultimately desired mass production of the CHEMFETs, which is essentially based on photolithography. The introduction of such a hydrogel layer [22,23], in which an aqueous buffered solution of salts can be absorbed, between the gate oxide and the sensing membrane eliminates the interference of CO2 on the CHEMFET response. Moreover, this stabilizes the potential developed in the sensing membrane. Plasticized PVC membranes, that contain an ionophore, are widely used as sensing membranes. Leakage of plasticizer to the contacting aqueous solution and weak adhesion of the membrane to the ISFET prompted the search for other polymer membranes like polyurethane, silicone rubber, polystyrene, polyamide and several polyacrylates [20,23,24].
The development of a CHEMFET technology, based on chemically attached poly(2-hydroxyethyl methacryalate) (polyHEMA) hydrogel between a hydrophobic membrane and the gate oxide layer, solved the problem of the thermodynamically ill-defined membrane-gate interface and suppresses interference from CO2. This novel architecture of FETs allows the design of new chemical sensors based on polymeric membranes containing molecular receptors. CHEMFETs selective to K+ [20,25-27], Na+ [28-30], Ag+ [31], some transition metals cations (Pb2+, Cd2+) [32-34] and some anions (NO3-) [35-37] have been developed. The limited lifetime of these sensors resulted from the leaching out of electroactive components, i.e. the ligand and the ionic sites, from the membrane phase to the sample solution. To increase the sensor durability, electroactive components with an enhanced lipophilicity could be applied, but a more efficient method is covalent anchoring of these components to the membrane matrix. Application of membranes containing covalently bond ionophore and covalently bond ionic sites improved efficiently the durability of so-called durable CHEMFETs [26-29].
REFET
The use of a conventional reference electrode limited seriously the application of ISFETs with respect to the small size and low cost. Therefore the development of a miniature reference electrode made with the IC-compatible technology (reference field effect transistor - REFET) is of great interest for the wide-spread use of these sensors.
One of the approaches to solve this problem is the on-chip fabrication of an Ag/AgCl electrode with IC-compatible techniques, including a gel filled cavity and a porous silicon plug [38-42]. However, all the constructions have the disadvantage of a liquid-filled internal cavity with associated limited lifetime because of leakage of reference solution. A better approach to the problem of the reference electrode could be the application of two chemically unequally sensitive ISFETs in a differential mode with a common quasi-reference electrode (QRE) (e.g., a metal wire Pt), which can be easily integrated on the silicon chip [43-46]. This device have the additional advantage that external disturbances, influencing both ISFETs (light and temperature sensitivity) will be reduced. Since the accuracy of differential measurements depends on the difference in the ion sensitivity of both ISFETs, although complete insensitivity of one ISFET (REFET) would be preferred. Such a reference FET should in a ideal case show insensitivity to all species present in the sample solution.
Originally, the oxide gate surface show pH sensitivity, owing to the presence of hydroxyl groups, which can dissociate and can be protonated. It was reported that the complete elimination of the pH-sensitive groups by chemical monolayer modification cannot be achieved [47]. However, the pH sensitivity can ce suppressed by attaching to the gate surface an ion-blocking hydrophobic polymeric layer. In this modification the polymer was chemically bounded to the gate surface, which results in a long lifetime of the device. For ion-blocking layers, a stable attachment has been realized by plasma deposition [48-52]. However, potential variations with electrolyte compositions for such modified REFETs were observed [53]. Moreover, the deposition is limited to very thin polymeric layers because of diminishing electrical sensitivity (transconductance) with increasing insulator thickness [5].
In contrast to ion-blocking polymers, modification of REFETs with ion-unblocking (conductive) polymers would have the advantage of an equal transconductance of the REFET and ISFET [54,55]. Unfortunately, such ion-unblocking hydrophobic membranes result in a short lifetime of the sensor, if they are not chemically anchored to the surface. Taking this account, ISFETs have been modified in order to prepare REFETs with polymeric membranes which are covalently linked to the gate oxide surface [56,57].
Two types of REFET structures can be distinguished with respect to the penetration of ions into the polymeric layer, resulting in two different mechanisms of the REFET operation. In a non-ion-blocking REFET structure there are ion exchange between the solution and the polymer; consequently a thermodynamical equilibrium between ions in the solution and in the polymer is achieved and the membrane electrical potential is a membrane potential. In an ion-blocking REFET structure this ion exchange is negligible and in this case the electrical potential measured is a surface potential resulting from reversible ion-complexation reactions at the surface of the polymer.
Our contribution in the development of the CHEMFETs
Our scientific and research activity in the field of electrochemical sensors was initiated in the beginning of 80-ties, mainly on classical membrane ion selective electrodes. We have investigated many systems of cation- and anion-selective membranes based on neutral and charged ionophores in plasticized PVC.
In the last decade we started the research projects devoted to the application of FET transducers in electrochemical sensors. We have used the experience obtained earlier, concerning molecular recognition by organic receptors, in the transduction of chemical information. Our interests involved the development of new ion-selective CHEMFETs and reference field effect transistor. In the figure 3, we showed the pH response of our REFET based on polyHEMA covered gate oxide FET.
Figure 3. pH response of REFET based on membrane containing calixspherand.
The polyHEMA intermediate hydrogel layer was covered with a sensing PVC/DOS membrane containing calixspherand and lipophilic borate salt. Almost ideal insensitivity of these devices in the wide pH range and stable potential in the wide range of activity of different ions in water solution was observed.
We have developed few anion-sensitive CHEMFETs. The most important was: nitrite- and perchlorate- selective sensors based on PVC membranes with uranyl salophen and calix[4]arene receptors respectively. Good selectivities versus interfering anions and responses with a slope 32 and 42 mV/pX- in a wide linear range were obtained (Fig. 4a).
Click here for Picture 4a
Click here for Picture 4b
Figure 4. a) Nitrite, perchlorate response curves of NO2- -selective CHEMFETs (1) and ClO4- -selective CHEMFETs (2) in 0.1mol l-1NaNO3, pH=4.5. b), Potassium response curve of K+-selective CHEMFET in 0.1mol l-1NaNO3, pH=4.5
Other projects are devoted to the development of durable cation-sensitive CHEMFETs (e.g. K+-selective CHEMFET based on PVC membrane containing valinomycin presented in the Fig. 4b).
Conclusions
The application of field effect transistors (FETs) as transducers in electrochemical sensors was first described in 1970 by Bergveld and is in present a well-known transducing element. These devices can transduce an amount of charge present on the surface of the gate insulator, that is immersed in an aqueous solution, into a corresponding drain current. The main reason for this fast expantion was the introduction of IC-technology in the construction of these sensors, that allowed to simple mass fabrication.
This modern technology provide the possibility to design a multi-ion sensors integrated with his reference cell (REFET). These sensors has a small size, robustness, use only very small amounts of, often expensive, ion-sensing compoounds.
References:
1. Bergveld P., IEEE Trans. Biomed. Eng., BME-17, 70 (1970).
2. Bousse L., and Bergveld P., Sens. Actuators, 6, 65 (1984).
3. van den Berg A., Bergveld P., Reinhoudt D.N., and Sudholter E.J.R., Sens. Actuators, 8, 129 (1985).
4. Reinhoudt D.N., and Sudholter E.J.R., Adv. Mater., 2, 23 (1990).
5. Bousse L., de Rooij N.F., and Bergveld P., IEEE Trans. Electron. Devices, ED- 30, 1263 (1983).
6. Moss S.D., Janata J., and Johnson C.C., Anal. Chem., 47, 2238 (1975).
7. McBride P.T., Janata J., Comte P.A., Moss S.D., and Johnson C.C., Anal. Chim. Acta, 101, 239 (1978).
8. Buck R.P., and Hackleman D.E., Anal. Chem., 49, 2315 (1977).
9. Matsuo T., Nakajima H., Osa T., and Anzai J., Proc. Transducers '85, Philadelphia, 1985, 250.
10. Janata J., and Huber R.J., Ion-Selective Electrode Rev., 1, 31 (1979).
11. Sibbald A., IEE Proc., 130, 233 (1983).
12. Sudholter E.J.R., van der Wal P.D., Skowrońska-Ptasińska M., van den Berg A., Bergveld P., and Reinhoudt D.N., Recl. Trav. Chim. Pays-Bas, 109, 222 (1990).
13. Oesch U., Caras S., and Janata J., Anal. Chem., 53, 1983 (1981).
14. Sibbald A., Whalley P.D., and Covington A.K., Anal. Chim. Acta, 159, 47 (1984).
15. Fogt E.J., Untereker D.F., Norenberg M.S., and Meyerhoff M.E., Anal. Chem., 57, 1995 (1985).
16. van den Vlekkert H.H., Decroux M., and de Rooij N.F., Proc, Transducers '87, Tokyo, 1987, 730.
17. Dror M., Bergs E.A., and Rhodes R.K., Sens. Actuators, 11, 23 (1987).
18. Talma A.G., Volders J.P.G.M., Ligtenberg H.C.G., Dost L., Bouwmeester H.J.M., and Boekema B., Sens. Actuators, 10, 35 (1987).
19. Blackburn G.F., and Janata J., J. Electrochem. Soc., 129, 2580 (1982).
20. van der Wal P., Skowrońska-Ptasińska M., van den Berg A., Bergveld P., Sudholter E.J.R., and Reinhoudt D.N., Anal. Chim. Acta, 231, 41 (1990).
21. Harrison D.J., Teclemariam A., and Cunningham L., Anal. Chem, 61, 246 (1989).
22. Sudholter E.J.R., van der Wal P., Skowrońska-Ptasińska M., van den Berg A., Bergveld P., and Reinhoudt D.N., Anal. Chim. Acta, 230, 59 (1990).
23. Fiedler U., and Ruzicka J., Anal. Chim. Acta, 67, 179 (1973).
24. Mascini M., and Palozzi F., Anal. Chim. Acta, 73, 375 (1974).
25. Brzózka Z., Holterman H.A.J., Honig G.W.N., Verkerk U.H., van den Vlekkert H.H., Engbersen J.F.J., and Reinhoudt D.N., Sens. Actuators, 18-19, 38 (1994).
26. Reinhoudt D.N., Engbersen J.F.J., Brzózka Z., van den Vlekkert H.H., Honig G.W.N., Holterman H.A.J., and Verkerk U.H., Anal. Chem., 66, 3618 (1994).
27. van der Wal P.D., Sudholter E.J.R., and Reinhoudt D.N., Anal. Chim. Acta, 245, 159 (1991).
28. Brunink J.A.J., Haak J.R.,Bomer J.G., Reinhoudt D.N., McKervey M.A., and Harris S.J., Anal. Chim. Acta, 254, 75 (1991).
29. Brunink J.A.J., Bomer J.G., Engbersen J.F.J., Verboom W., and Reinhoudt D.N., Sens. Actuators, 15-16, 195 (1993).
30. Brunink J.A.J., Lugtenberg R.J.W., Brzózka Z., Engbersen J.F.J., and Reinhoudt D.N., J. Electroanal. Chem., 378, 185 (1994).
31. Brzózka Z., Cobben P.L.H.M., Reinhoudt D.N., Edema J.J.H., Buter J., and Kellogg R.M., Anal. Chim. Acta, 273, 139 (1993).
32. Cobben P.L.H.M., Egberink R.J.M., Bomer J.G., Bergveld P., Verboom W., and Reinhoudt D.N., J. Am. Chem. Soc., 114, 10573 (1992).
33. Cobben P.L.H.M., Egberink R.J.M., Bomer J.G., Schouwenaar R., Brzózka Z., Bos M., Bergveld P., and Reinhoudt D.N., Anal. Chim. Acta, 276, 347 (1993).
34. Cobben P.L.H.M., Egberink R.J.M., Bomer J.G., Haak J.R., Bergveld P., and Reinhoudt D.N., Sens. Actuators, 6, 304 (1992).
35. Dumschat C., Fromer R., Rautschek H., Muller H., and Timpe H.-J., Anal. Chim. Acta, 243, 179 (1991).
36. Rocher V., Jaffrezic-Renault N., Perrot H., Chevalier Y., and Le Perchec P., Anal.Chim. Acta, 256, 251 (1992).
37. Stauthamer W.P.R.V., Engbersen J.F.J., Verboom W., and Reinhoudt D.N., Sens. Actuators, 17, 197 (1994).
38. Hochmair E.S., and Prohaska O., in W.H. Ko (Ed.), Implantable Sensors for Closed-Loop Prosthetic Systems, Futura, Mountkisco, NY, 1985, 652.
39. Prohaska O., Goiser A., Jachomowits F., Kohl F., and Olcaytug F., Proc. of the 2nd International Meeting on Chemical Sensors, Bordeaux, 1986, 652.
40. Smith R.L., and Scott D.C., Proc. of the Symposium on Biosensors, IEEE 84, CH-2068-5, 61 (1984).
41. Smith R.L., and Scott D.C., IEEE Trans. Biomed. Eng., BME 33, 83 (1986).
42. Margules G.S., Hunter C.M., and McGregor D.C., Med. Biol. Eng. Comput., 21, 1 (1983).
43. Comte P.A., and Janata J., Anal. Chim. Acta, 101, 247 (1978).
44. Hanazoto Y., and Shiono S., Chemical Sensors (Anal. Chem. Symp. Ser., Vol. 17), 513 (1983).
45. Kuisl M., and Klein M., Messtechnik, 36, 48 (1983).
46. Bergveld P., van den Berg A., van der Wal P.D., Skowrońska-Ptasińska M., Suholter E.J.R., and Reinhoudt D.N., Sens. Actuators, 18, 307 (1989).
47. van den Berg A., Bergveld P., Reinhoudt D.N., and Sudholter E.J.R., Sens. Actuators, 8, 129 (1985).
48. Nakajima H., Esashi M., and Matsuo T., J. Electroanal. Chem. Soc., 129, 141 (1982).
49. Fujihira M., Fukui M., and Osa T., J. Electroanal. Chem., 106, 413 (1980).
50. Tahara S., Yoshii M., and Oka S., Chem. Lett., 1982, 307.
51. Matsuo T., and Nakajima H., Sens. Actuators, 5, 293 (1984).
52. Kimura J., Kuriyama T., and Kawana Y., Sens. Actuators, 9, 373 (1980).
53. Matsuo T., and Esashi M., Extended Abstractsof the Electrochemical Society Spring Meeting, Seattle, WA, 1978, 202.
54. Kimura J., Kuriyama T., and Kawana Y., Proc. Transducers '85, Philadelphia, 1985, 152.
55. Cammann K., and Honold F., Proc. of the 2nd International Meeting on Chemical Sensors, Bordeaux, 1986, 554.
56. Skowrońska-Ptasińska M., van der Wal P., van den Berg A., Bergveld P., Sudholter E.J.R., and Reinhoudt D.N., Anal. Chim. Acta, 230, 67 (1990).
57. van den Berg A., van der Wal P., Ptasiński D., Sudholter E.J.R., Reinhoudt D.N., and Bergveld P., Proc. of the 2nd International Meeting on Chemical Sensors, Bordeaux, 1986, 419.
>
