- Email: [email protected]
A behavioral macromodel of the ISFET in SPICE
Sensors and Actuators B 62 Ž2000. 182–189 www.elsevier.nlrlocatersensorb
A behavioral macromodel of the ISFET in SPICE Sergio Martinoia ) , Giuseppe Massobrio Department of Biophysical and Electronic Engineering (DIBE), UniÕersity of GenoÕa, Via all’Opera Pia 11 r A, 16145 GenoÕa, Italy Received 2 August 1999; received in revised form 27 October 1999; accepted 28 October 1999
Abstract Physico-chemical models of the ISFET ŽIon-Sensitive Field-Effect Transistor. were developed by the authors in the past, as SPICE built-in models ŽBIOSPICE.. This approach has some drawbacks, i.e., the need of availability of the program source, a deep knowledge of the code subroutines and structure, and the need of compiling the whole program when a new model has to be implemented or when modifications to the models have to be made. To overcome these drawbacks, a more general and user-friendly approach is presented. It consists of a behavioral macromodel that can be used in conjunction with the most commercial SPICE versions. The behavior of the proposed macromodel has been validated by comparing the results with those obtained by BIOSPICE physico-chemical models and experimental measurements. The proposed macromodel is shown to operate also under subthreshold conditions that can be considered as a promising operating mode for large multisensor ISFET-based integrated systems. q 2000 Published by Elsevier Science S.A. All rights reserved. Keywords: Chemical transducers; Biomedical transducers; SPICE; Modeling; Simulation
1. Introduction Silicon technology is widely used for sensor development; it offers the advantage to integrate, on the same chip, different sensors and their related signal processing circuits. Moreover, computer aids in the form of electronic circuit simulation and design programs such as SPICE w1,2x, have evolved in response to the evolution of complex and sophisticated modern electronic systems, and they can be adapted to design semiconductor sensors. The program SPICE we refer to, has built-in models for most semiconductor devices, but no model for semiconductor sensors is implemented. This lack was considered extensively in the past when we developed and introduced models of ISFETs ŽIon-Sensitive Field-Effect Transistors. into SPICE version 2G ŽUniversity of California, Berkeley, CA, USA. as physico-chemical built-in models w3–7x. This approach yielded to a modified version of the original SPICE-2G, called BIOSPICE, suitable to handle ISFET-based sensors as new built-in devices. This operation required the modification of several subroutines of the original code and the writing of new ones. This approach implies the availability of the program source, a deep knowledge of the code )
Corresponding author. Tel.: q0039-10-3532-251; fax: q0039-103532-133; e-mail: [email protected]
subroutines and structure and it is strictly linked to a particular version of SPICE. Thus, these requirements prevent a broad use of such a tool to design ISFET-based integrated systems and do not allow many users to easily modify the models. In this paper, we are presenting a macromodel for the ISFET Žin particular a pH-sensitive FET. to be used in conjunction with HSPICE w8x, even if it can be easily adapted to other commercial versions of SPICE, such as PSPICE ŽMicroSim . or SPICE3 ŽUniversity of California, Berkeley, CA, USA.. We have chosen HSPICE because of its facilities, capabilities, and the availability of a large set of MOSFET models Žwhich are the starting structure of the ISFET. some of them operating also in the subthreshold mode. 2. ISFET macromodel formulation The simplest ISFET is a pH-sensitive FET ŽFig. 1. with its sensitive surface made of an insulator layer Že.g., Si 3 N4 , Al 2 O 3 , Ta 2 O5 . exposed to an electrolyte solution Žsee for a review Refs. w9–12x.. A p-type semiconductor and an Si 3 N4 insulator placed directly in an aqueous electrolyte solution Ž1:1 salt solution; e.g., NaCl. are considered. The response of the ISFET to pH can be explained by considering Hq-specific binding sites at the insulator surface w13x.
0925-4005r00r$ - see front matter q 2000 Published by Elsevier Science S.A. All rights reserved. PII: S 0 9 2 5 - 4 0 0 5 Ž 9 9 . 0 0 3 7 7 - 9
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
Fig. 1. Sketch of an n-channel ISFET structure Žfor explanations see the text..
Physico-chemical models were developed w3–7x as SPICE built-in models, resulting in an equation system which fully characterizes the ISFET behavior. A more general and user-friendly model, derived from the previously developed physico-chemical models, has been implemented in HSPICE as a macromodel. To achieve this goal, we have considered the ISFET as two fully uncoupled Žas far as the physical point of view is concerned. stages: an electronic stage Ži.e., the MOSFET which is the starting structure of the ISFET. and an electrochemical stage Ži.e., the electrolyte–insulator interface.. This assumption contradicts the condition of charge neutrality of the structure of Fig. 1, given by:
so q sd q ss s 0
Ž 1.
where so , sd , and ss are the charge densities at the electrolyte–insulator interface, in the diffuse layer and in the semiconductor, respectively. On the other hand, by considering ss constant in respect of pH, and by assuming it much smaller than so and sd , w14x, Eq. Ž1. reduces to:
so q sd s 0
183
where ´ w is the permittivity of the electrolyte; c bulk is the ion concentration in the electrolyte; NSil and NNit are the surface densities of the silanol sites and of the primary amine sites, respectively; K A , K B , K N , are the binding site dissociation constants; H b is the proton concentration in the bulk electrolyte; weo is the potential of the electrolyte–insulator interface; wgd is the potential across the diffusion layer ŽGouy–Chapman layer. as indicated in Fig. 1; V T s kTrq is the thermal voltage; fa Ž weo , pH. and f b Ž weo , pH. are self explaining setting functions. The approach we have formulated leads to the ISFET equivalent circuit Žmacromodel. shown in Fig. 2, where the capacitor Ceq , which takes into account the Gouy– Chapman or diffuse layer Ž CGouy . and the Helmholtz layer Ž C Helm ., is defined as: Ceq s
CGouy C Helm CGouy q C Helm
Ž 5.
The dependence of the charge density of the diffuse layer wd wEq. Ž3.x on the potential of the electrolyte–insulator interface weo can be written also in the form:
sd s yso s yCeq weo
Ž 6.
On the other hand, the Gouy–Chapman and Helmholtz capacitances can be written as follows. For the Helmholtz capacitance w4,16x: ´ IHP ´ OHP C Helm s WL Ž 7. ´ OH P d IHP q ´ IHP d OHP where W and L, are the ISFET channel width and length, respectively; ´ IHP and ´ OHP are the inner and outer Helmholtz plane permittivities, respectively; d IHP and d OHP are the insulator–nonhydrated ion and the insulator–hydrated ion distances, respectively.
Ž 2.
and therefore the electrochemical stage can be considered as uncoupled from the electronic stage. From the site-binding theory and the electrical doublelayer theory w3,13,15,16x, we obtain:
(
sd s 8 ´ w kTc bu lk sinh
so s qNSil
wgd
ž / 2V T
H b2 exp y2
ž
H b2 exp y2
ž ž
H b2 exp y
=
H b2 exp
ž
y
weo VT
weo VT
weo VT
/
/ /
s a sinh weo VT
/
ž
Ž 3.
2VT
y KA K B
q K A H b2 exp y
q KN
wgd
ž / weo VT
/
q KA K B
0
q qNNit
0
s qNSil fa Ž weo ,pH . q qNNit f b Ž weo ,pH .
Ž 4.
Fig. 2. Equivalent electric circuit of the ISFET structure. The series capacitances CGo uy and C Helm are substituted by the equivalent capacitor Ceq in the macro-model circuit definition Žfor explanations see the text..
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
184
3. HSPICE macromodel definition
Fig. 3. HSPICE subcircuit block and external connections for the ISFET macro-model. R s reference electrode; Dsdrain; Sssource; Bs bulk; pH ssolution pH value.
For the Gouy–Chapman capacitance, by considering the sinh approximated by its argument Žfor wgd < 2VT . w14x: CGouy s
(
Esd
E
Ewgd
(8 ´
s
Ewgd
w kTc bu lk
2VT
(8 ´
w kTc bu lk
sinh
wgd
ž / 2V T
Ž 8.
When Eqs. Ž7. and Ž8. are introduced into Eq. Ž5., then Eqs. Ž4. and Ž6. give the potential of the electrolyte–insulator interface, i.e., q weo s NSil fa Ž weo ,pH . q NNit f b Ž weo ,pH . Ž 9. Ceq Eq. Ž9. states the potential weo is modeled as a nonlinear voltage-controlled voltage source, which depends, in its turn, both on pH and weo itself. The electronic stage is simply modeled by using the available MOSFET models.
Eqs. Ž5. and Ž9. have been translated into an equivalent circuit Žthe electrochemical stage of the ISFET., which has been coupled to an n-channel MOSFET Žthe electronic stage of the ISFET. resulting into a behavioral macromodel which defines the ISFET model ŽFig. 2. we implemented in HSPICE. The equivalent circuit of the ISFET, which models the electrochemical behavior, can be used as a new ‘‘kind’’ of electronic device for designing ‘‘intelligent’’ pH sensors or ISFET-based microsystems. At user’s convenience, the macromodel has been defined, in HSPICE, as a subcircuit block. Fig. 3 shows the outer connections of the subcircuit block, where R, D, S, B, stand for the reference electrode, the drain, the source, and the bulk connections, respectively; pH stands for the connection for the emulated pH-independent input source. The pH-independent source is a chemical input signal modeled by an independent voltage source connected to a dummy resistor. The macromodel uses this voltage Ži.e., the pH value. as the electrochemical source that controls the potential weo in Eq. Ž9.. The complete HSPICE behavioral macromodel Žsubcircuit block. for an Si 3 N4-gate ISFET is detailed in Appendix A. 4. Simulation results The developed macromodel has been extensively tested, and the simulation results have been compared both with experimental data and with the previously validated physico-chemical model results w3–7x.
Fig. 4. HSPICE simulations: threshold voltage variations of an Si 3 N4 -gate ISFET Žmacro-model. as a function of pH at different ratios of amine sites vs. silanol sites Ž NSil and NNit are measured in numberrm2 .. The limiting case with no amine sites corresponds to an SiO 2-gate ISFET.
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
185
Fig. 5. Input simulated characteristics of the Si 3 N4 -gate ISFET under test compared with experimental data at pH s 4, 7, 10 for Vds s 0.1 V.
Fig. 4 shows the threshold voltage variations of an Si 3 N4-gate ISFET Žmacromodel. as a function of pH at different ratios of amine sites vs. silanol sites w4x. The simulation results point out the non-linearity of the Si 3 N4gate ISFET at low concentration of amine sites Žcf. the limiting case of the SiO 2-gate ISFET. as reported in literature w16,17x. Input and output characteristics of other types of ISFETs Že.g., Al 2 O 3 , Ta 2 O5-gate ISFETs. can be simulated by changing the parameter values of the surface site densities and of the dissociation constants w3,18x.
Eventually, resetting HSPICE parameters for convergence is required. Fig. 5 shows the simulated input characteristics of the Si 3 N4-gate ISFET under test compared with experimental data at three different pH values ŽpH s 4, 7, 10. and at Vds s 0.1 V. It should be noted that the .MODEL statement of HSPICE and the electrochemical parameter values have been adapted for the specific ISFET Ži.e., an Si 3 N4-gate ISFET with double insulating layer and stoichiometric silicon nitride as sensitive layer w19–21x.. The physical and
Fig. 6. HSPICE input simulated characteristics of an Si 3 N4 -gate ISFET compared with the previously validated model Žphysico-chemical model. implemented in BIOSPICE w3,4x at pH s 4, 7, 10 for Vds s 0.5 V. For the HSPICE input file see Appendix A.
186
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
Fig. 7. HSPICE simulations: input characteristics of an Si 3 N4 -gate ISFET in the subthreshold region compared with experimental measurements. The model used for the MOSFET Želectronic stage of the ISFET. is identified by Levels 34.
geometrical parameters have been obtained by standard parameter extraction procedures performed on specific test structures related to the specific technology used for the ISFET under test. Moreover, for some electrochemical parameters, not-optimized parameter extraction procedures have been utilized. Other electrochemical parameters, such as the reaction constants Ž K A , K B , K N . and the total density of the binding sites, have been taken from the literature. Fig. 6 shows the simulated input characteristics at Vds s 0.5 V and pH s 4, 7, 10 obtained by the proposed behavioral macromodel Žsee Appendix A. and by the previously developed BIOSPICE physical-model w4x: a good agreement is obtained both for the curve shape and for the average sensitivity. Finally, Fig. 7 shows the HSPICE simulation results of the electrochemical behavior of the ISFET in the subthreshold region compared to experimental data: also in this operating condition, the model shows a good agreement with the measurements and gives a sensitivity close to that obtained in the strong inversion region. Small deviations from the measured data have to be related to the fact that simulation results were obtained by using default MOSFET parameters for the sub-threshold condition. In fact, we did not have any actual data Žcoming from parameter extraction procedures. about the sub-threshold condition for the ISFET under test.
SPICE electronic network analysis program. The presented results show a good agreement with experimental data and previously validated physical models proving the feasibility of the proposed approach for modeling the electrochemical characteristics of ISFET-based biosensors. The developed macromodel can be easily extended for simulating non-ideal behaviors w5x and temperature dependence w6x. In addition, similar macromodels can be envisaged for other bioelectronic devices and can be implemented into different versions of SPICE. As a final remark, this methodological approach permits to join the computational robustness of the SPICE program with the possibility of simulating complex circuits involving hybrid devices Že.g., chemical- and bio-sensors. and signal conditioning electronics. The presented example Žcf. Appendix A. can be easily utilized, by other interested researchers, as a guideline for developing their own specific models.
5. Discussions and conclusions
Appendix A
In this paper we have presented a simple and powerful approach to developing computer models of bioelectronic devices w9–12x such as ISFETs. This approach relies on the
The complete HSPICE input file for an Si 3 N4-gate ISFET is reported Žthe simulation result is shown in Fig. 6.. The introduced electrochemical parameters are listed
Acknowledgements The authors wish to thank Dr. Leandro Lorenzelli for helpful discussions. The Si 3 N4-gate ISFETs we utilized were kindly supplied by the Microsensor and Integration System Division of IRSTrITC ŽVia Sommariva, Pante` di Povo 38050 Trento, Italy..
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
and their meanings and physical dimensions are reported. The .MODEL parameter values for the MOSFET Žthe electronic stage of the ISFET. and the electrochemical parameter values Žthe electrochemical stage of the ISFET. are related to a specific ISFET technology realized by the Microsensor and Integration System Division of IRSTrITC
187
ŽTrento, Italy.. The HSPICE parameters for convergence problems have been set for the specific example. If another sensitive layer for the ISFET is considered, some electrochemical parameters have to be changed Ži.e., the dissociation constants and the surface site densities. and the parameter values for convergence have to be adjusted.
))))))))))))))))))))))))))))))))))))))))))))))))))) FILE: ISFET MACROMODEL ))))))))))))))))))))))))))))))))))))))))))))))))))) U Behavioral macromodel for the ISFET with two U kinds of binding sites: silanol and amine sites U By Sergio Martinoia and Giuseppe Massobrio U Bioelectronics Laboratory, Dept. of Biophysical and Electronic Eng. U Via Opera Pia 11A, 16145, Genova, ITALY U email: [email protected] U September 1998 ))))))))))))))))))))))))))))))))))))))))))))))))))) U PARAMETER LIST U General constants: U q s electronic charge wCx U k s Boltzmann’s constant wJrKx U T s Absolute temperature wKx U NAv s Avogadro’s constant w1rmolex U ISFET geometrical parameters: U dihp s distance between the Inner Helmholtz Plane ŽIHP. and the ISFET surface wmx U dohp s distance between the Outer Helmholtz Plane ŽIHP. and the ISFET surface wmx U ISFET electrochemical parameters: U Ka s positive dissociation constant wmolerlx U Kb s negative dissociation constant wmolerlx U Kn s dissociation constant for amine sites wmolerlx U Nsil s silanol Žor oxide. surface site density warm2x U Nnit s amine surface site density warm2x U Cbulks electrolyte concentration w1rmolesx U epsihps relative permittivity of the Inner Helmholtz layer U epsohps relative permittivity of the Outer Helmholtz layer U epsw s relative permittivity of the bulk electrolyte solution U Reference-electrode electrochemical parameters: U Eabs s absolute potential of the standard hydrogen electrode wVx U Erel s potential of the ref. electrode ŽAgrAgCl. relative to the hydrogen electrode wVx U Phims work function of the metal back contact r electronic charge wVx U Philj s liquid-junction potential difference between the ref. solution and the electrolyte wVx U Chieos surface dipole potential wVx ))))))))))))))))))))))))))))))))))))))))))))))))))) .OPTION LIST ingolds 0 post probe q absmoss 1e y 15 dcsteps 1000 nopiv q absv s 1e y 15 relv s 1e y 12 absi s 1e y 15 q gmindcs 1e y 24 itl1 s 1000 converge accurate q methods gear lvltims 2 itl5 s 10000 delmaxs 1e y 15 q dv s 0.2 .PARAM q k s 1.38e y 23 T s 300 eps0 s 8.85e y 12 q Ka s 15.8 Kb s 63.1e y 9 Kn s 1e y 10 q Nsil s 3.0e18 Nnit s 2.0e18 q Cbulks 0.1 U Beginning of the sub-circuit definition
188
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
U sssssssssssssssssssssssssssssssssssssssssssss
.SUBCKT ISFET 6 1 3 4 101 drain < ref.el < source < bulk < pH input q q s 1.6e y 19 NAv s ’6.023e23U 1e3’ q epsw s 78.5 epsihps 32 epsohps 32 q dihp s 0.1n dohp s 0.3n Cbulks 0.1 q Eabs s 4.7 Phims 4.7 Erel s 0.200 Chieo s 3e y 3 Philj s 1e y 3 q ET s ’qrŽkU T.’ q sq s ’sqrtŽ8U eps0U epswU kU T.’ q Cb s ’NAv U Cbulk’ q KK s ’KaU Kb’ q Ch s ’ŽŽeps0U epsihpU epsohp.rŽepsohpU dihp q epsihpU dohp..’ q Cd s ’ŽsqU ETU 0.5.U sqrtŽCb.’ q Ceq s ’1rŽ1rCd q 1rCh.’ Eref 1 10 VOL s ’Eabs-Phim-Erelq Chieoq Philj’ Ceq 10 2 C s ’1rŽ1rCd q 1rCh.’ EP1 46 0 VOL s ’logŽKK. q 4.6U VŽ101.’ RP1 46 0 1G EP2 23 0 VOL s ’logŽKa. q 2.3U VŽ101.’ RP2 23 0 1G EPH 2 10 VOL s ’ŽqrCeq.U ŽNsilU ŽŽexpŽy2U VŽ2,10.U ET. y expŽVŽ46...rŽexpŽy2U VŽ2,10.U ET. qexpŽVŽ23..U expŽy1U VŽ2,10.U ET. q expŽVŽ46.... q NnitU ŽŽexpŽy1U VŽ2,10.U ET..r ŽexpŽy1U VŽ2,10.U ET. q ŽKnrKa.U expŽVŽ23.....’ RpH 101 0 1K MIS 6 2 3 4 MISFET L s 18u W s 804u NRS s 5 NRD s 5 ))))))))))))))))))))))))))))))))))))))))))))))))))) .MODEL MISFET NMOS LEVELs 2 q VTO s 7.99E y 01 LAMBDAs 7.59E y 03 RSH s 3.5E q 01 TOX s 86E y 9 q UO s 6.53E q 02 TPG s 0 q UEXPs 7.64E y 02 NSUBs 3.27E q 15 NFS s 1.21E q 11 q NEFFs 3.88 VMAXs 5.35E q 04 DELTAs 1.47 LD s 2.91E y 06 q UCRITs 7.97E q 04 XJ s 6.01E y 09 CJ s 4.44E y 4 IS s 1E y 11 q CJSWs 5.15E y 10 PHI s 5.55E y 01 GAMMAs 9.95E y 01 q MJ s 0.395 MJSWs 0.242 PB s 0.585 ))))))))))))))))))))))))))))))))))))))))))))))))))) .ENDS ISFET U sssssssssssssssssssssssssssssssssssssssssssss U Beginning of the example circuit XIS 100 1 0 0 200 ISFET Vbias 1 0 DC 1.5 VpH 200 0 DC 10 Vd 110 0 DC 0.5 Vid 110 100 DC 0 .OP debug .DC Vbias 0.0 4 0.1 .PRINT DC VŽ1,XIS.2. VŽXIS.2,0. VŽXIS.23. VŽXIS.46. VŽ1. IŽVid. .PROBE DC VŽ1,XIS.2. VŽXIS.2,0. VŽXIS.23. VŽXIS.46. VŽ1. IŽVid. .END U
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w2x G. Massobrio, P. Antognetti, Semiconductor Device Modeling with SPICE, 2nd edn., McGraw-Hill, New York, USA, 1993. w3x M. Grattarola, G. Massobrio, S. Martinoia, Modeling Hq-Sensitive FETs with SPICE, IEEE Trans. Electron Devices ED-39 Ž4. Ž1992. 813–819. w4x G. Massobrio, S. Martinoia, M. Grattarola, Use of SPICE for
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
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modeling silicon-based chemical sensors, Sensors and Materials 6 Ž2. Ž1994. 101–123. S. Martinoia, M. Grattarola, G. Massobrio, Modelling non-ideal behaviours in Sensitive FETs with SPICE, Sensors and Actuators B 7 Ž1992. 561–564. G. Massobrio, S. Martinoia, Modelling the ISFET behaviour under temperature variations using BIOSPICE, Electronics Letters 32 Ž10. Ž1996. 936–938. S. Martinoia, L. Lorenzelli, G. Massobrio, P. Conci, A. Lui, Temperature effects on the ISFET behaviour: simulations and measurements, Sensors and Actuators B Ž1998. 60–68. HSPICE User’s Manual, Meta-Software, Campbell, CA, USA, 1992. J. Janata, R.J. Huber, Solid State Chemical Sensors, Academic Press, Orlando, USA, 1985. P. Bergveld, A. Sibbald, Analytical and Biomedical Applications of ISFETs, Elsevier, Amsterdam, Netherlands, 1988. S.M. Zse, Semiconductor Sensors, Wiley, New York, USA, 1994. M. Grattarola, G. Massobrio, Bioelectronics Handbook: Mosfets, Biosensors, and Neurons, McGraw-Hill, New York, USA, 1998. D.E. Yates, S. Levine, T.W. Healy, Site-binding model of the electrical double layer at the oxiderwater interface, J. Chem. Soc. Farady Trans. 70 Ž1974. 1807–1818. L. Bousse, N.F. de Rooij, P. Bergveld, Operation of chemically sensitive field-effect Sensor as a function of the insulator-electrolyte interface, IEEE Trans. Electron Devices ED-30 Ž10. Ž1983. 1263– 1270. J.A. Davis, R.O. James, J.O. Leckie, Surface ionization and complexation at the oxiderwater interface, Journal of Colloid and Interface Science 63 Ž3. Ž1978. 480–499. C.D. Fung, P.W. Cheung, W.H. Ko, A generalized theory of an electrolyte–insulator–semiconductor field-effect transistor, IEEE Trans. Electron Devices ED-33 Ž1. Ž1986. 3–18. D.L. Harame, L. Bousse, J. Schott, J.D. Meindl, Ion sensing devices with silicon nitride and borosilicate glass insulator, IEEE Trans. Electron Devices ED-34 Ž10. Ž1987. 1700–1707. J.C. van Kerkhof, J.C.T. Eijkel, P. Bergveld, ISFET response on a stepwise change in electrolyte concentration at constant pH, Sensors and Actuators B 18-19 Ž1994. 56–59. A. Lui, B. Margesin, V. Zanini, M. Zen, G. Soncini, S. Martinoia, A
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test chip for ISFETrCMNOS technology development, Proc. ICMTS96, Trento, 1996. w20x A. Cambiaso, S. Chiarugi, M. Grattarola, L. Lorenzelli, A. Lui, B. Margesin, S. Martinoia, V. Zanini, M. Zen, An Hq-FET-based system for on-line detection of micro-organism in waters, Sensors and Actuators B 24–25 Ž1996. 218–221, Elsevier Science, Losanna, Switzerland. w21x S. Martinoia, L. Lorenzelli, G. Massobrio, B. Margesin, A. Lui, A CAD system for developing chemical sensor-based microsystems with an ISFET-CMOS compatible technology, Sensor and Materials 11 Ž5. Ž1999. 32–49, MYU Tokyo, Japan.
Biographies Sergio Martinoia was born in Sanremo, Italy, in 1964. He received the Laurea degree in Electronic Engineering from the University of Genova in 1989 and the Ph.D. degree in Electronic Bioengineering in 1993. At present, he is Assistant Professor of Biomedical Technologies at the University of Genova and he is currently working at the Department of Biophysical and Electronic Engineering ŽDIBE.. His research interests include: solid-state sensor modeling and applications, development of multichannel microelectrode based systems for electrophysiological measurements, signal processing of electrophysiological signals. Giuseppe Massobrio received the Laurea degree in Electronic Engineering from the University of Genova, Italy, in 1976. He is Research Associate in the Department of Biophysical and Electronic Engineering ŽDIBE. at the University of Genova. Since 1976 he has worked on semiconductor power device modeling, and circuit design and simulation. Since 1987 he has been working on modeling semiconductor-based biosensors, and neuronal structures. His extensive background in microelectronic device modeling includes teaching and research activities. In the fields of bioelectronics and of semiconductor device modeling he has contributed several papers to international journals. He is coauthor of the books: ‘‘Semiconductor DeÕice Modeling with SPICE’’ Ž1988, 1993 2nd ed.. published by McGraw-Hill, and ‘‘Bioelectronics Handbook: Mosfets, Biosensors, and Neurons’’ Ž1998. published by McGraw-Hill.
A behavioral macromodel of the ISFET in SPICE Sergio Martinoia ) , Giuseppe Massobrio Department of Biophysical and Electronic Engineering (DIBE), UniÕersity of GenoÕa, Via all’Opera Pia 11 r A, 16145 GenoÕa, Italy Received 2 August 1999; received in revised form 27 October 1999; accepted 28 October 1999
Abstract Physico-chemical models of the ISFET ŽIon-Sensitive Field-Effect Transistor. were developed by the authors in the past, as SPICE built-in models ŽBIOSPICE.. This approach has some drawbacks, i.e., the need of availability of the program source, a deep knowledge of the code subroutines and structure, and the need of compiling the whole program when a new model has to be implemented or when modifications to the models have to be made. To overcome these drawbacks, a more general and user-friendly approach is presented. It consists of a behavioral macromodel that can be used in conjunction with the most commercial SPICE versions. The behavior of the proposed macromodel has been validated by comparing the results with those obtained by BIOSPICE physico-chemical models and experimental measurements. The proposed macromodel is shown to operate also under subthreshold conditions that can be considered as a promising operating mode for large multisensor ISFET-based integrated systems. q 2000 Published by Elsevier Science S.A. All rights reserved. Keywords: Chemical transducers; Biomedical transducers; SPICE; Modeling; Simulation
1. Introduction Silicon technology is widely used for sensor development; it offers the advantage to integrate, on the same chip, different sensors and their related signal processing circuits. Moreover, computer aids in the form of electronic circuit simulation and design programs such as SPICE w1,2x, have evolved in response to the evolution of complex and sophisticated modern electronic systems, and they can be adapted to design semiconductor sensors. The program SPICE we refer to, has built-in models for most semiconductor devices, but no model for semiconductor sensors is implemented. This lack was considered extensively in the past when we developed and introduced models of ISFETs ŽIon-Sensitive Field-Effect Transistors. into SPICE version 2G ŽUniversity of California, Berkeley, CA, USA. as physico-chemical built-in models w3–7x. This approach yielded to a modified version of the original SPICE-2G, called BIOSPICE, suitable to handle ISFET-based sensors as new built-in devices. This operation required the modification of several subroutines of the original code and the writing of new ones. This approach implies the availability of the program source, a deep knowledge of the code )
Corresponding author. Tel.: q0039-10-3532-251; fax: q0039-103532-133; e-mail: [email protected]
subroutines and structure and it is strictly linked to a particular version of SPICE. Thus, these requirements prevent a broad use of such a tool to design ISFET-based integrated systems and do not allow many users to easily modify the models. In this paper, we are presenting a macromodel for the ISFET Žin particular a pH-sensitive FET. to be used in conjunction with HSPICE w8x, even if it can be easily adapted to other commercial versions of SPICE, such as PSPICE ŽMicroSim . or SPICE3 ŽUniversity of California, Berkeley, CA, USA.. We have chosen HSPICE because of its facilities, capabilities, and the availability of a large set of MOSFET models Žwhich are the starting structure of the ISFET. some of them operating also in the subthreshold mode. 2. ISFET macromodel formulation The simplest ISFET is a pH-sensitive FET ŽFig. 1. with its sensitive surface made of an insulator layer Že.g., Si 3 N4 , Al 2 O 3 , Ta 2 O5 . exposed to an electrolyte solution Žsee for a review Refs. w9–12x.. A p-type semiconductor and an Si 3 N4 insulator placed directly in an aqueous electrolyte solution Ž1:1 salt solution; e.g., NaCl. are considered. The response of the ISFET to pH can be explained by considering Hq-specific binding sites at the insulator surface w13x.
0925-4005r00r$ - see front matter q 2000 Published by Elsevier Science S.A. All rights reserved. PII: S 0 9 2 5 - 4 0 0 5 Ž 9 9 . 0 0 3 7 7 - 9
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
Fig. 1. Sketch of an n-channel ISFET structure Žfor explanations see the text..
Physico-chemical models were developed w3–7x as SPICE built-in models, resulting in an equation system which fully characterizes the ISFET behavior. A more general and user-friendly model, derived from the previously developed physico-chemical models, has been implemented in HSPICE as a macromodel. To achieve this goal, we have considered the ISFET as two fully uncoupled Žas far as the physical point of view is concerned. stages: an electronic stage Ži.e., the MOSFET which is the starting structure of the ISFET. and an electrochemical stage Ži.e., the electrolyte–insulator interface.. This assumption contradicts the condition of charge neutrality of the structure of Fig. 1, given by:
so q sd q ss s 0
Ž 1.
where so , sd , and ss are the charge densities at the electrolyte–insulator interface, in the diffuse layer and in the semiconductor, respectively. On the other hand, by considering ss constant in respect of pH, and by assuming it much smaller than so and sd , w14x, Eq. Ž1. reduces to:
so q sd s 0
183
where ´ w is the permittivity of the electrolyte; c bulk is the ion concentration in the electrolyte; NSil and NNit are the surface densities of the silanol sites and of the primary amine sites, respectively; K A , K B , K N , are the binding site dissociation constants; H b is the proton concentration in the bulk electrolyte; weo is the potential of the electrolyte–insulator interface; wgd is the potential across the diffusion layer ŽGouy–Chapman layer. as indicated in Fig. 1; V T s kTrq is the thermal voltage; fa Ž weo , pH. and f b Ž weo , pH. are self explaining setting functions. The approach we have formulated leads to the ISFET equivalent circuit Žmacromodel. shown in Fig. 2, where the capacitor Ceq , which takes into account the Gouy– Chapman or diffuse layer Ž CGouy . and the Helmholtz layer Ž C Helm ., is defined as: Ceq s
CGouy C Helm CGouy q C Helm
Ž 5.
The dependence of the charge density of the diffuse layer wd wEq. Ž3.x on the potential of the electrolyte–insulator interface weo can be written also in the form:
sd s yso s yCeq weo
Ž 6.
On the other hand, the Gouy–Chapman and Helmholtz capacitances can be written as follows. For the Helmholtz capacitance w4,16x: ´ IHP ´ OHP C Helm s WL Ž 7. ´ OH P d IHP q ´ IHP d OHP where W and L, are the ISFET channel width and length, respectively; ´ IHP and ´ OHP are the inner and outer Helmholtz plane permittivities, respectively; d IHP and d OHP are the insulator–nonhydrated ion and the insulator–hydrated ion distances, respectively.
Ž 2.
and therefore the electrochemical stage can be considered as uncoupled from the electronic stage. From the site-binding theory and the electrical doublelayer theory w3,13,15,16x, we obtain:
(
sd s 8 ´ w kTc bu lk sinh
so s qNSil
wgd
ž / 2V T
H b2 exp y2
ž
H b2 exp y2
ž ž
H b2 exp y
=
H b2 exp
ž
y
weo VT
weo VT
weo VT
/
/ /
s a sinh weo VT
/
ž
Ž 3.
2VT
y KA K B
q K A H b2 exp y
q KN
wgd
ž / weo VT
/
q KA K B
0
q qNNit
0
s qNSil fa Ž weo ,pH . q qNNit f b Ž weo ,pH .
Ž 4.
Fig. 2. Equivalent electric circuit of the ISFET structure. The series capacitances CGo uy and C Helm are substituted by the equivalent capacitor Ceq in the macro-model circuit definition Žfor explanations see the text..
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
184
3. HSPICE macromodel definition
Fig. 3. HSPICE subcircuit block and external connections for the ISFET macro-model. R s reference electrode; Dsdrain; Sssource; Bs bulk; pH ssolution pH value.
For the Gouy–Chapman capacitance, by considering the sinh approximated by its argument Žfor wgd < 2VT . w14x: CGouy s
(
Esd
E
Ewgd
(8 ´
s
Ewgd
w kTc bu lk
2VT
(8 ´
w kTc bu lk
sinh
wgd
ž / 2V T
Ž 8.
When Eqs. Ž7. and Ž8. are introduced into Eq. Ž5., then Eqs. Ž4. and Ž6. give the potential of the electrolyte–insulator interface, i.e., q weo s NSil fa Ž weo ,pH . q NNit f b Ž weo ,pH . Ž 9. Ceq Eq. Ž9. states the potential weo is modeled as a nonlinear voltage-controlled voltage source, which depends, in its turn, both on pH and weo itself. The electronic stage is simply modeled by using the available MOSFET models.
Eqs. Ž5. and Ž9. have been translated into an equivalent circuit Žthe electrochemical stage of the ISFET., which has been coupled to an n-channel MOSFET Žthe electronic stage of the ISFET. resulting into a behavioral macromodel which defines the ISFET model ŽFig. 2. we implemented in HSPICE. The equivalent circuit of the ISFET, which models the electrochemical behavior, can be used as a new ‘‘kind’’ of electronic device for designing ‘‘intelligent’’ pH sensors or ISFET-based microsystems. At user’s convenience, the macromodel has been defined, in HSPICE, as a subcircuit block. Fig. 3 shows the outer connections of the subcircuit block, where R, D, S, B, stand for the reference electrode, the drain, the source, and the bulk connections, respectively; pH stands for the connection for the emulated pH-independent input source. The pH-independent source is a chemical input signal modeled by an independent voltage source connected to a dummy resistor. The macromodel uses this voltage Ži.e., the pH value. as the electrochemical source that controls the potential weo in Eq. Ž9.. The complete HSPICE behavioral macromodel Žsubcircuit block. for an Si 3 N4-gate ISFET is detailed in Appendix A. 4. Simulation results The developed macromodel has been extensively tested, and the simulation results have been compared both with experimental data and with the previously validated physico-chemical model results w3–7x.
Fig. 4. HSPICE simulations: threshold voltage variations of an Si 3 N4 -gate ISFET Žmacro-model. as a function of pH at different ratios of amine sites vs. silanol sites Ž NSil and NNit are measured in numberrm2 .. The limiting case with no amine sites corresponds to an SiO 2-gate ISFET.
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
185
Fig. 5. Input simulated characteristics of the Si 3 N4 -gate ISFET under test compared with experimental data at pH s 4, 7, 10 for Vds s 0.1 V.
Fig. 4 shows the threshold voltage variations of an Si 3 N4-gate ISFET Žmacromodel. as a function of pH at different ratios of amine sites vs. silanol sites w4x. The simulation results point out the non-linearity of the Si 3 N4gate ISFET at low concentration of amine sites Žcf. the limiting case of the SiO 2-gate ISFET. as reported in literature w16,17x. Input and output characteristics of other types of ISFETs Že.g., Al 2 O 3 , Ta 2 O5-gate ISFETs. can be simulated by changing the parameter values of the surface site densities and of the dissociation constants w3,18x.
Eventually, resetting HSPICE parameters for convergence is required. Fig. 5 shows the simulated input characteristics of the Si 3 N4-gate ISFET under test compared with experimental data at three different pH values ŽpH s 4, 7, 10. and at Vds s 0.1 V. It should be noted that the .MODEL statement of HSPICE and the electrochemical parameter values have been adapted for the specific ISFET Ži.e., an Si 3 N4-gate ISFET with double insulating layer and stoichiometric silicon nitride as sensitive layer w19–21x.. The physical and
Fig. 6. HSPICE input simulated characteristics of an Si 3 N4 -gate ISFET compared with the previously validated model Žphysico-chemical model. implemented in BIOSPICE w3,4x at pH s 4, 7, 10 for Vds s 0.5 V. For the HSPICE input file see Appendix A.
186
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
Fig. 7. HSPICE simulations: input characteristics of an Si 3 N4 -gate ISFET in the subthreshold region compared with experimental measurements. The model used for the MOSFET Želectronic stage of the ISFET. is identified by Levels 34.
geometrical parameters have been obtained by standard parameter extraction procedures performed on specific test structures related to the specific technology used for the ISFET under test. Moreover, for some electrochemical parameters, not-optimized parameter extraction procedures have been utilized. Other electrochemical parameters, such as the reaction constants Ž K A , K B , K N . and the total density of the binding sites, have been taken from the literature. Fig. 6 shows the simulated input characteristics at Vds s 0.5 V and pH s 4, 7, 10 obtained by the proposed behavioral macromodel Žsee Appendix A. and by the previously developed BIOSPICE physical-model w4x: a good agreement is obtained both for the curve shape and for the average sensitivity. Finally, Fig. 7 shows the HSPICE simulation results of the electrochemical behavior of the ISFET in the subthreshold region compared to experimental data: also in this operating condition, the model shows a good agreement with the measurements and gives a sensitivity close to that obtained in the strong inversion region. Small deviations from the measured data have to be related to the fact that simulation results were obtained by using default MOSFET parameters for the sub-threshold condition. In fact, we did not have any actual data Žcoming from parameter extraction procedures. about the sub-threshold condition for the ISFET under test.
SPICE electronic network analysis program. The presented results show a good agreement with experimental data and previously validated physical models proving the feasibility of the proposed approach for modeling the electrochemical characteristics of ISFET-based biosensors. The developed macromodel can be easily extended for simulating non-ideal behaviors w5x and temperature dependence w6x. In addition, similar macromodels can be envisaged for other bioelectronic devices and can be implemented into different versions of SPICE. As a final remark, this methodological approach permits to join the computational robustness of the SPICE program with the possibility of simulating complex circuits involving hybrid devices Že.g., chemical- and bio-sensors. and signal conditioning electronics. The presented example Žcf. Appendix A. can be easily utilized, by other interested researchers, as a guideline for developing their own specific models.
5. Discussions and conclusions
Appendix A
In this paper we have presented a simple and powerful approach to developing computer models of bioelectronic devices w9–12x such as ISFETs. This approach relies on the
The complete HSPICE input file for an Si 3 N4-gate ISFET is reported Žthe simulation result is shown in Fig. 6.. The introduced electrochemical parameters are listed
Acknowledgements The authors wish to thank Dr. Leandro Lorenzelli for helpful discussions. The Si 3 N4-gate ISFETs we utilized were kindly supplied by the Microsensor and Integration System Division of IRSTrITC ŽVia Sommariva, Pante` di Povo 38050 Trento, Italy..
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
and their meanings and physical dimensions are reported. The .MODEL parameter values for the MOSFET Žthe electronic stage of the ISFET. and the electrochemical parameter values Žthe electrochemical stage of the ISFET. are related to a specific ISFET technology realized by the Microsensor and Integration System Division of IRSTrITC
187
ŽTrento, Italy.. The HSPICE parameters for convergence problems have been set for the specific example. If another sensitive layer for the ISFET is considered, some electrochemical parameters have to be changed Ži.e., the dissociation constants and the surface site densities. and the parameter values for convergence have to be adjusted.
))))))))))))))))))))))))))))))))))))))))))))))))))) FILE: ISFET MACROMODEL ))))))))))))))))))))))))))))))))))))))))))))))))))) U Behavioral macromodel for the ISFET with two U kinds of binding sites: silanol and amine sites U By Sergio Martinoia and Giuseppe Massobrio U Bioelectronics Laboratory, Dept. of Biophysical and Electronic Eng. U Via Opera Pia 11A, 16145, Genova, ITALY U email: [email protected] U September 1998 ))))))))))))))))))))))))))))))))))))))))))))))))))) U PARAMETER LIST U General constants: U q s electronic charge wCx U k s Boltzmann’s constant wJrKx U T s Absolute temperature wKx U NAv s Avogadro’s constant w1rmolex U ISFET geometrical parameters: U dihp s distance between the Inner Helmholtz Plane ŽIHP. and the ISFET surface wmx U dohp s distance between the Outer Helmholtz Plane ŽIHP. and the ISFET surface wmx U ISFET electrochemical parameters: U Ka s positive dissociation constant wmolerlx U Kb s negative dissociation constant wmolerlx U Kn s dissociation constant for amine sites wmolerlx U Nsil s silanol Žor oxide. surface site density warm2x U Nnit s amine surface site density warm2x U Cbulks electrolyte concentration w1rmolesx U epsihps relative permittivity of the Inner Helmholtz layer U epsohps relative permittivity of the Outer Helmholtz layer U epsw s relative permittivity of the bulk electrolyte solution U Reference-electrode electrochemical parameters: U Eabs s absolute potential of the standard hydrogen electrode wVx U Erel s potential of the ref. electrode ŽAgrAgCl. relative to the hydrogen electrode wVx U Phims work function of the metal back contact r electronic charge wVx U Philj s liquid-junction potential difference between the ref. solution and the electrolyte wVx U Chieos surface dipole potential wVx ))))))))))))))))))))))))))))))))))))))))))))))))))) .OPTION LIST ingolds 0 post probe q absmoss 1e y 15 dcsteps 1000 nopiv q absv s 1e y 15 relv s 1e y 12 absi s 1e y 15 q gmindcs 1e y 24 itl1 s 1000 converge accurate q methods gear lvltims 2 itl5 s 10000 delmaxs 1e y 15 q dv s 0.2 .PARAM q k s 1.38e y 23 T s 300 eps0 s 8.85e y 12 q Ka s 15.8 Kb s 63.1e y 9 Kn s 1e y 10 q Nsil s 3.0e18 Nnit s 2.0e18 q Cbulks 0.1 U Beginning of the sub-circuit definition
188
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
U sssssssssssssssssssssssssssssssssssssssssssss
.SUBCKT ISFET 6 1 3 4 101 drain < ref.el < source < bulk < pH input q q s 1.6e y 19 NAv s ’6.023e23U 1e3’ q epsw s 78.5 epsihps 32 epsohps 32 q dihp s 0.1n dohp s 0.3n Cbulks 0.1 q Eabs s 4.7 Phims 4.7 Erel s 0.200 Chieo s 3e y 3 Philj s 1e y 3 q ET s ’qrŽkU T.’ q sq s ’sqrtŽ8U eps0U epswU kU T.’ q Cb s ’NAv U Cbulk’ q KK s ’KaU Kb’ q Ch s ’ŽŽeps0U epsihpU epsohp.rŽepsohpU dihp q epsihpU dohp..’ q Cd s ’ŽsqU ETU 0.5.U sqrtŽCb.’ q Ceq s ’1rŽ1rCd q 1rCh.’ Eref 1 10 VOL s ’Eabs-Phim-Erelq Chieoq Philj’ Ceq 10 2 C s ’1rŽ1rCd q 1rCh.’ EP1 46 0 VOL s ’logŽKK. q 4.6U VŽ101.’ RP1 46 0 1G EP2 23 0 VOL s ’logŽKa. q 2.3U VŽ101.’ RP2 23 0 1G EPH 2 10 VOL s ’ŽqrCeq.U ŽNsilU ŽŽexpŽy2U VŽ2,10.U ET. y expŽVŽ46...rŽexpŽy2U VŽ2,10.U ET. qexpŽVŽ23..U expŽy1U VŽ2,10.U ET. q expŽVŽ46.... q NnitU ŽŽexpŽy1U VŽ2,10.U ET..r ŽexpŽy1U VŽ2,10.U ET. q ŽKnrKa.U expŽVŽ23.....’ RpH 101 0 1K MIS 6 2 3 4 MISFET L s 18u W s 804u NRS s 5 NRD s 5 ))))))))))))))))))))))))))))))))))))))))))))))))))) .MODEL MISFET NMOS LEVELs 2 q VTO s 7.99E y 01 LAMBDAs 7.59E y 03 RSH s 3.5E q 01 TOX s 86E y 9 q UO s 6.53E q 02 TPG s 0 q UEXPs 7.64E y 02 NSUBs 3.27E q 15 NFS s 1.21E q 11 q NEFFs 3.88 VMAXs 5.35E q 04 DELTAs 1.47 LD s 2.91E y 06 q UCRITs 7.97E q 04 XJ s 6.01E y 09 CJ s 4.44E y 4 IS s 1E y 11 q CJSWs 5.15E y 10 PHI s 5.55E y 01 GAMMAs 9.95E y 01 q MJ s 0.395 MJSWs 0.242 PB s 0.585 ))))))))))))))))))))))))))))))))))))))))))))))))))) .ENDS ISFET U sssssssssssssssssssssssssssssssssssssssssssss U Beginning of the example circuit XIS 100 1 0 0 200 ISFET Vbias 1 0 DC 1.5 VpH 200 0 DC 10 Vd 110 0 DC 0.5 Vid 110 100 DC 0 .OP debug .DC Vbias 0.0 4 0.1 .PRINT DC VŽ1,XIS.2. VŽXIS.2,0. VŽXIS.23. VŽXIS.46. VŽ1. IŽVid. .PROBE DC VŽ1,XIS.2. VŽXIS.2,0. VŽXIS.23. VŽXIS.46. VŽ1. IŽVid. .END U
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w2x G. Massobrio, P. Antognetti, Semiconductor Device Modeling with SPICE, 2nd edn., McGraw-Hill, New York, USA, 1993. w3x M. Grattarola, G. Massobrio, S. Martinoia, Modeling Hq-Sensitive FETs with SPICE, IEEE Trans. Electron Devices ED-39 Ž4. Ž1992. 813–819. w4x G. Massobrio, S. Martinoia, M. Grattarola, Use of SPICE for
S. Martinoia, G. Massobrior Sensors and Actuators B 62 (2000) 182–189
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modeling silicon-based chemical sensors, Sensors and Materials 6 Ž2. Ž1994. 101–123. S. Martinoia, M. Grattarola, G. Massobrio, Modelling non-ideal behaviours in Sensitive FETs with SPICE, Sensors and Actuators B 7 Ž1992. 561–564. G. Massobrio, S. Martinoia, Modelling the ISFET behaviour under temperature variations using BIOSPICE, Electronics Letters 32 Ž10. Ž1996. 936–938. S. Martinoia, L. Lorenzelli, G. Massobrio, P. Conci, A. Lui, Temperature effects on the ISFET behaviour: simulations and measurements, Sensors and Actuators B Ž1998. 60–68. HSPICE User’s Manual, Meta-Software, Campbell, CA, USA, 1992. J. Janata, R.J. Huber, Solid State Chemical Sensors, Academic Press, Orlando, USA, 1985. P. Bergveld, A. Sibbald, Analytical and Biomedical Applications of ISFETs, Elsevier, Amsterdam, Netherlands, 1988. S.M. Zse, Semiconductor Sensors, Wiley, New York, USA, 1994. M. Grattarola, G. Massobrio, Bioelectronics Handbook: Mosfets, Biosensors, and Neurons, McGraw-Hill, New York, USA, 1998. D.E. Yates, S. Levine, T.W. Healy, Site-binding model of the electrical double layer at the oxiderwater interface, J. Chem. Soc. Farady Trans. 70 Ž1974. 1807–1818. L. Bousse, N.F. de Rooij, P. Bergveld, Operation of chemically sensitive field-effect Sensor as a function of the insulator-electrolyte interface, IEEE Trans. Electron Devices ED-30 Ž10. Ž1983. 1263– 1270. J.A. Davis, R.O. James, J.O. Leckie, Surface ionization and complexation at the oxiderwater interface, Journal of Colloid and Interface Science 63 Ž3. Ž1978. 480–499. C.D. Fung, P.W. Cheung, W.H. Ko, A generalized theory of an electrolyte–insulator–semiconductor field-effect transistor, IEEE Trans. Electron Devices ED-33 Ž1. Ž1986. 3–18. D.L. Harame, L. Bousse, J. Schott, J.D. Meindl, Ion sensing devices with silicon nitride and borosilicate glass insulator, IEEE Trans. Electron Devices ED-34 Ž10. Ž1987. 1700–1707. J.C. van Kerkhof, J.C.T. Eijkel, P. Bergveld, ISFET response on a stepwise change in electrolyte concentration at constant pH, Sensors and Actuators B 18-19 Ž1994. 56–59. A. Lui, B. Margesin, V. Zanini, M. Zen, G. Soncini, S. Martinoia, A
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test chip for ISFETrCMNOS technology development, Proc. ICMTS96, Trento, 1996. w20x A. Cambiaso, S. Chiarugi, M. Grattarola, L. Lorenzelli, A. Lui, B. Margesin, S. Martinoia, V. Zanini, M. Zen, An Hq-FET-based system for on-line detection of micro-organism in waters, Sensors and Actuators B 24–25 Ž1996. 218–221, Elsevier Science, Losanna, Switzerland. w21x S. Martinoia, L. Lorenzelli, G. Massobrio, B. Margesin, A. Lui, A CAD system for developing chemical sensor-based microsystems with an ISFET-CMOS compatible technology, Sensor and Materials 11 Ž5. Ž1999. 32–49, MYU Tokyo, Japan.
Biographies Sergio Martinoia was born in Sanremo, Italy, in 1964. He received the Laurea degree in Electronic Engineering from the University of Genova in 1989 and the Ph.D. degree in Electronic Bioengineering in 1993. At present, he is Assistant Professor of Biomedical Technologies at the University of Genova and he is currently working at the Department of Biophysical and Electronic Engineering ŽDIBE.. His research interests include: solid-state sensor modeling and applications, development of multichannel microelectrode based systems for electrophysiological measurements, signal processing of electrophysiological signals. Giuseppe Massobrio received the Laurea degree in Electronic Engineering from the University of Genova, Italy, in 1976. He is Research Associate in the Department of Biophysical and Electronic Engineering ŽDIBE. at the University of Genova. Since 1976 he has worked on semiconductor power device modeling, and circuit design and simulation. Since 1987 he has been working on modeling semiconductor-based biosensors, and neuronal structures. His extensive background in microelectronic device modeling includes teaching and research activities. In the fields of bioelectronics and of semiconductor device modeling he has contributed several papers to international journals. He is coauthor of the books: ‘‘Semiconductor DeÕice Modeling with SPICE’’ Ž1988, 1993 2nd ed.. published by McGraw-Hill, and ‘‘Bioelectronics Handbook: Mosfets, Biosensors, and Neurons’’ Ž1998. published by McGraw-Hill.