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Temperature dependence of Buried Channel Ion Sensitive Field Effect Transistors Roman Novitski1, Hila Einati1 and Yosi Shacham-Diamand1,2. 1 Dept. of Physical Electronics, Eng. Faculty, and the Univ. Res. Inst. for Nano Science and NanoTechnologies, Tel-Aviv University, Ramat-Aviv 69978, Israel 2 The Dept. of Applied Chemistry, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan, *Corresponding author: H.Einati, Phone: +972-3-6408064, fax: +972-3-6423508 Email: [email protected] Abstract In this paper we describe the temperature dependence of Buried Channel (BC) ISFET. The device response depends on the temperature; hence, temperature variations can cause erroneous readings. A theoretical model describing the temperature dependence of BCISFET and a theoretical solution to eliminate the signal variations due to temperature changes is presented here. The suggested solution is based on an inverter containing nBC-ISFET and p-BC-ISFET. The influence of various parameters on the operation of the inverter and its sensitivity are investigated. We discuss the influence of self assembled monolayers on the operation of the inverter. 1 Introduction Ion Sensitive Field Effect Transistors (ISFETs) have been investigated in the last four decades for various chemical and biological sensing applications. Biological interactions or chemical reactions that cause potential changes at the insulator/electrolyte interface of the ISFET can be detected by a shift of the threshold voltage of the transistor [1, 2]. Most ISFETs fabricated today are based on enhancement n-type or p-type MOSFETs, which conduct current in a conducting channel as a result of an interface inversion charge. Until now few papers have been published on characterization of a Buried Channel (BC) ISFET [3, 4], which conducts current through a conducting channel implanted beneath the SiO2 dielectric layer. The BC-ISFET is typically realized by impurities implanted into a substrate of opposite doping. This implant alters the threshold voltage, and significantly changes the operating characteristics of the device. Depending on the doping density distribution, physical dimensions and bias conditions, the device can appear in a number of operating modes including inversion, depletion, pinch-off, and accumulation. This is important for biosensing applications which typically operate at low frequencies. There are two main advantages for a BC-ISFET over an enhancement ISFET. The first is its ability to operate under zero gate voltage, as there is no need to create a conducting channel by inverting the carrier type under the dielectric. The second advantage of BC-ISFET is its better noise performance at lower frequencies, since current conduction occurs in the bulk of the semiconductor decreasing the influence of interface traps at the Si-SiO2 interface. Fig. 1 shows both devices, the enhancement p-type ISFET and the p-BC-ISFET. 2 The operational mechanism of the ISFET originates from the pH sensitivity of the inorganic gate oxide, such as SiO2, Al2O3, Si3Ni4, or Ta2O5. This mechanism is a surface phenomenon which can be explained by the site binding theory [5]. Surface hydroxyl groups react with the analyte in an acidic or a basic way, resulting in a corresponding surface charge and potential. ISFETs are also very sensitive to temperature variations, which can cause large readout errors as a result of threshold voltage shifts due to the temperature changes. The temperature variations influence both the output signal of the transistor and the pH itself. The temperature behavior of an ISFET was theoretically and experimentally studied [69]. It was found to be a complex function related to the reference electrode, measured electrolyte, interfacial potentials and the solid-state device itself. It strongly depends on the operating point of the device. The results of these investigations showed that ISFETs have an athermal operating point, an isothermal point, at which the drain current is nearly temperature independent. Efforts have been invested [10-16] on various techniques of temperature compensation using interface circuit design. Aw and Cheung [10] showed a simple method to improve the thermal stability of an ISFET by determining experimentally an athermal point; a point where the output voltage is almost independent of the temperature. However, the athermal operating point of the ISFET varies with the pH of the solution. Another work [11] was focused on the hybrid differential pair of ISFET-MOSFET incorporating a PN junction diode or integration of an ISFET as part of a standard operational amplifier. Comprising an ISFET/MOSFET source-coupled differential pair, fabricated with the same technology, can provide certain immunity on the temperature sensitivity of the 3 semiconductor part of ISFET, or TCsemi; but the required size of the ISFET gate might be much larger than that of the MOSFET, resulting in mismatches in the input differential pair and the bias currents. Poghossian et al. [8, 9] realized that a pH ISFET-based temperature sensor can be used in a differential set-up consisting of two identical pH ISFETs, having different operating points. Another technique employing similar concept is to use two threshold voltage (Vth) extractor circuits [12]. The first extractor is an ISFET which gives the pH reading, and the second is a depletion-type MOSFET which provides the temperature compensation. The output differential stage gives the difference between the threshold voltages of ISFET and depletion-type MOSFET. Chan and Chen [13] used a nonlinear temperature compensation method that is based on the theoretical work for formulating a body effect based ISFET drain current expression, a unified temperature dependent ISFET threshold voltage expression and the use of iterative method for solving design parameters in nonlinear equations. The final result of which is the optimum biasing current IB required for the ISFET to work around the athermal point in different pH buffer solutions. Electrolyte with pH=7 was used as a reference in this method. This paper presents a model describing the operational mechanism and the temperature dependence of the BC-ISFETs. An electrical circuit is suggested to compensate the temperature influence and improve the performance of the sensor. Modeling: 4 In an electrode–electrolyte system, charges accumulate at the electrode and the surface area of the electrolyte. Due to the abundance of charge carriers in the electrode, the ions are immobile and fixed on the surface of the electrode. Helmholtz modeled this behavior as a pure capacitor, marked as CH. However, this model only partially described the real behavior of the double layer and was accurate over a small range of potentials. Gouy and Chapman suggested an additional model which describes the diffuse layer. This layer is not compact and has of variable thickness. The ions in it are free to move. This layer accounts for effects of applied potential and electrolyte concentration. The capacitance of this layer is signed as Cdiff. Though the Gouy–Chapman model provides an estimate of potential distribution around the electrode–electrolyte interface, it over estimates the interface charges. Hence Stern suggested a serial connection of the two capacitors. The total capacitance is called the double layer capacitance, Cdl. For solutions with high ionic strengths or high bias voltages Cdiff becomes very large and Cdl is approximately equal to CH [17] The sensitivity of the ISFETs to potential changes of aqueous solutions can be explained with the aid of the electrical double layer and the site-binding theories [5]. The potential change at the insulator/electrolyte interface is determined mainly by exchange of hydrogen ions between the electrolyte and reactive sites at the insulator surface. In the case of Si3N4 (on top of SiO2) sensing layer we assume that silanol (Si-OH) sites and primary amine sites (NH2) are present on the insulator surface after immersing in electrolyte solution. The surface reactions of silicon nitride layers are: K SiOH 2 SiOH H (1) K SiOH SiO H (2) 5 K 3 N SiNH SiNH 2 H (3) K+, K - and KN+ are the dissociation constants of the surface reactions. The total charge on the insulator surface, σ0, is determined by the density of the donor (SiO-) and acceptor (SiOH2+ and SiNH3+) sites on the surface: 0 qSiOH 2 SiO SiNH 3 (4) The total charge in the system must be zero, therefore the following condition must hold: mos d 0 ox 0 (5) Where σMOS is the total charge of the semiconductor, σd and σ0 are the charges of the diffuse layer and the insulator surface, respectively. σox is the effective charge located at the oxide-silicon interface, which consists of a fixed charge inside the insulator and an interface trap charge. The flat-band voltage of a BC-ISFET can be expressed by: V fb E ref lj eo _ fb e ( s Eg 2q B ) (6) where E ref is the potential of the reference electrode relative to the vacuum, lj is the liquid-junction potential difference between the reference solution and the electrolyte, χe is the surface dipole potential, χs is the silicon affinity, Eg is the bandgap of the silicon and B is the difference between the Fermi energy inside the conducting channel and the intrinsic Fermi energy. Fig. 2 shows the charge and potential distributions in p-BC-ISFET immersed into Phosphate Buffer Saline (PBS) solution. PBS was chosen since it is a common electrolyte in biological experiments. 6 Assuming the depletion approximation, the threshold voltage of the p-BC-ISFET is given by: X N d Vbi 1 Xi 1 2q s N a N d Vbi (7) Vth _ P V fb _ P qN a i Na Nd Na Nd 2 s Cins s Cins Where Vfb_P is the flat band voltage of p-BC-ISFET, Na and Nd are the acceptor and donor concentrations, respectively. Xi is the implantation depth, εs is the permittivity of the semiconductor, Cins is the insulator capacitance, Vbi is the built-in voltage and q is the electron charge. The sensitivity of the BC-ISFET is defined by the linear dependence dφeo/dpHB, where φeo is the potential of the electrolyte-insulator interface and equals to the difference between the gate and Helmholtz potentials (φo - φg). pHB is the pH at the bulk electrolyte. High performance ISFETs show sensitivity of 58 mV/pH. However, one of the major problems of the ISFETs is temperature instability. The threshold voltage of the device can change not only as a result of pH variations, but due to temperature changes. The temperature coefficient of the threshold voltage is defined as its derivative with respect to the temperature. There are two contributions to it; one stems from the chemical parameters of the system (TCchem.), and another one from the semiconductor part of the device (TCsemi). The electrolyte-insulator interface potential, φeo, is directly related to the temperature through the thermal voltage KbT/q, where Kb is Boltzmann constant, T is the temperature and q is the electron charge. The equilibrium constants Kx in accordance to [18]: 7 K x T K0e qE KbT 300 [ K x 300] T (8) Where Kx(300) is the equilibrium constant at 300oC. The standard chemical potentials of the insulator surface species are assumed to be temperature independent; therefore, binding sites densities are constant with temperature. Assuming an Ag/AgCl reference electrode with filling solution of 3.5 M KCl, the temperature dependence of the potential Eref can be written as [18]: Eref T 4.905 1.4 10 4 T T0 (9) Where To=298.16 K. and 4.905 V is the work function of the electrode relative to vacuum. The liquid-junction potential for the Ag/AgCl electrode is assumed [19] as: lj T lj T0 10 5 T T0 (10) The temperature coefficient value of 10-5[V/K] holds for a liquid junction potential of lj T0 3mV . The surface dipole potential of the solution is assumed to be dependent on temperature through the relation [19]: e T e T0 1 e 0.86 log I 0.4 10 3 T T0 1 e T0 (11) Where I is the ionic strength of the solution, and the temperature coefficient (0.4·10-3 V/K) applies to an aqueous solution. The temperature dependence on the semiconductor parameters is described next. The bandgap of silicon is given by [20]: E g [eV ] 1.12 2.73 10 4 T 300 8 (12) The effective density of states in the conduction and valence bands are: 3 T 2 N c 3.2 1019 300 (13) 3 T 2 N v 1.8 1019 300 (14) The intrinsic carrier concentration is given by: ni N c N v e Eg 2 K bT B K bT N a ln q ni Vbi K bT N a N d ln 2 q ni (15) (16) (17) Where Nc and Nv are the effective densities of states of electrons in the conduction band and holes in the valence band, respectively, and Eg is the semiconductor band gap. Using equations 12-15 we can express the temperature dependence of B and Vbi given by equations 16 and 17 respectively. Their temperature coefficients can be expressed as follows: Na d B d K bT ln Eg dT dT q N N e 2 KbT c v K T N N d b ln a 2 d q dVbi ni dT dT Nc Nv K b ln q N a K b N a N d ln q N c N v 2.6576 10 4 V / oC 3.95 104 V / oC (18) (19) Using the last two results the temperature coefficient of the threshold voltage of BCISFET can be found, which is contributed by the semiconductor part of the device only. 9 Nd X q s N a N d dVbi d B 1 1 dE g TC semi i (20) N N dT C 2 V N N dT 2 q dT a d s ins bi a d As can be seen from the last result, TCsemi depends greatly on the fabrication parameters: conducting channel doping (Na), implantation depth (Xi), and insulator thickness (tox) on top of the channel. In view of the fact that ISFETs are temperature dependent, in the next section we propose a theoretical solution to eliminate the signal variations due to temperature changes. The suggested solution is based on an inverter configuration containing both nBC-ISFET and p-BC-ISFET. Inverter A BC-ISFET inverter configuration readout circuit with temperature compensation and body effect elimination is being investigated and simulated using MATLAB software. The BC-ISFET based inverter can operate in either one of the two modes: 1. Operation in the vicinity of the athermal point of BC-ISFET inverter. The output voltage is almost entirely insensitive to pH variations resulting from a temperature shift; only changing externally the hydrogen ion concentration will be reflected on the output voltage. 2. The output voltage is insensitive to the temperature variations and it follows the pH changes of the solution, whether they come from an external source or from a temperature shift. Another advantage of this circuit is its low voltage supplies VD and VS needed for the operation of the ISFETs, since they are of buried channel type. By the same reason 10 the circuit must exhibit better noise response at lower frequencies, since the flicker noise is very low compared to enhancement ISFETs. The structure of the complementary BC-ISFET inverter utilizing p-channel and nchannel ISFETs is shown in Fig. 3. Adding gate feedback is done by including an operational amplifier with a voltage source VD at the inverting terminal, and closing the loop with the output of the amplifier connected to the reference electrode. The output of the inverter is connected to the positive terminal of the operational amplifier. The reference electrode is used as the input terminal VIN for both ISFETs. The motivation for using this structure is to utilize the behavior of the threshold voltages of the devices. Both the threshold voltages of the p-BC-ISFET (Vth_P) and of n-BC-ISFET (Vth_N) increase with pH. Uplifting the temperature will increase Vth_P and decrease Vtn_N. Keeping the output voltage of the inverter constant (around VD), the input voltage (VIN=VOUT) can be adjusted according to the variations of Vth_P and Vth_N. Therefore, the input voltage tracks only the changes of the pH of the solution in spite of the temperature variations. When pH rises by ∆pH, the output voltage of the inverter raises by ∆V to VD+∆V. Operation-amplifier increase its output voltage accordingly and the gate voltage is adjusted so the output of the inverter goes back to the initial value VD. Assuming that both BC-ISFETs are made within the same process, the sensitivities of the sensors must be equal. Due to the series connection of transistors, the currents flowing through them are the same: I p f p Vth _ P V gate I n f n Vth _ N V gate 11 (21) When fp and fn are the current expressions for p-channel and n-channel devices, respectively. Since Vgate=VOUT, and ΔVth_P(ΔpH) = ΔVth_N(ΔpH), then in order to maintain equation 30 the output voltage must be adjusted accordingly: VOUT pH Vth _ P pH Vth _ N pH (22) Therefore, the sensitivity of the circuit is the same as the sensitivity of the individual sensors. In case the sensors have different sensitivities, a more elaborate analysis must be employed. The main reason for possible sensitivities mismatch in sensors is the different number of the binding sites. We’ll use approximate current equations of BC-MOSFETs developed by Tsividis [11] in order to derive the expression for sensitivity of the circuit. In saturation mode, the current is given by: W b Cins Vgs Vth Id L 1 2 2 (23) Where Cins X i Cins X i 1 s 2 s 1 1 (24) 4 Vbi (25) 2 s qN a ( d ) C ins (26) Cins - Insulator capacitance, Vbi - Built-in voltage in the channel- semiconductor substrate interface. X i - Implantation depth of the channel, N a d - Acceptor (donor) density of the substrate. 12 Since the current of both sensors is the same, then: W b _ n Cins _ n Vgs _ n Vth _ N W b _ p Cins _ p Vgs _ p Vth _ P (27) 2 n 2 p L n 1 n L p 1 p 2 2 Rearrangement of the expression gives: a W b _ n Cins _ n p W b _ p Cins _ p n VOUT Vth _ N VOUT VS Vth _ P / L 1 L 1 n p n p (28) Where W and L are the channel width and length of the transistor, respectively. Vs is the potential applied to the source. For simplicity we define a as: W b _ n Cins _ n p a 1 n L n W b _ p Cins _ p n / 1 p L p (29) Appling equation 29 into 28 to get: VOUT a Vth _ N Vth _ P VS (30) a 1 The change in the output voltage as a function of pH is given by: VOUT pH a Vth _ N pH Vth _ P pH a 1 (31) VOUT is the output voltage of the inverter, σn and σp are given by equation 24 for p-BCISFET and n-BC-ISFET, respectively. 13 Consequently, in case of equal sensitivities for both sensors described at equation 31 turns into equation 22. The same expression for sensitivity as (31) can be developed if both sensors are operating in the linear mode and VS=2VD is assumed. In that case a must be replaced with a 2 . Simulations: The performance of field effect devices varies with temperature. Hence, the influence of various parameters in the BC-ISFETs system was studied and simulated using the described model. The contribution of the semiconductor itself to the instability due to temperature alterations was simulated. The dependence of the channel doping, ion implantation depth and insulator thickness on temperature is presented. Current-voltage curves of BC-ISFETs for two pH values at three different temperatures are shown following by the threshold voltage dependence of pH at the same temperatures. Subsequently, we present the readout sensing signal based on the suggested inverter configuration at two different pH values. The BC-ISFETs fabrication parameters assumed in the simulations are as follows: for p-BC-ISFET the (W/L)P = 11, Xi_P=340 nm, tSiO2_P=tSi3N4_P= 50 nm. For n-BC-ISFET the (W/L)N = 2.5, Xi_N=375 nm, tSiO2_N=tSi3N4_N= 50 nm. The values of the voltage sources used are VS=0.4 V, and VD=0.2 V. Also ideal operational amplifier is assumed. Since there maybe a mismatch between the two BC-ISFETs of the inverter due to different number of silanol sites, the output signal of the inverter is shown as a function of NsilP/ NsilN ratio. The equilibrium constants of the chemical reactions are assumed to be 14 equal for both sensors. The number of silanol binding sites of n-BC-ISFET (NsilN) is kept constant, while that of p-BC-ISFET (NsilP) is varied between -20% up to +20% of NsilN. The sensors are assumed to be symmetrical by properly adjusting the W/L ratio (all other fabrication parameters are equal), so that a 2 1 . Next, we show the influence of the binding sites densities mismatch on the sensitivity of the circuit. Using the fabrication parameters of the circuit, we set the proportionality constant from equasion 31 between the two ISFETs to be a 2 0.56 . This means that the sensitivity of the p-BC-ISFET is more dominant in setting the sensitivity of the entire circuit, than that of the n-channel device. The suggested circuit is able to sense small pH variations due to temperature changes. Simulations indicating sensitivities to pH (T) at different working points of the inverter are shown. Results Fig. 4 shows the dependence of temperature coefficients in the main parameters of the transistor. Three different factors controlled by the fabrication process were examined: the channel doping, ion implantation depth and insulator thickness. It can be seen from fig. 4a that changing the channel doping from 1016 [cm-3] to 1017 [cm-3] at room temperature (300K), TCsemi varies from 2.05 to 1.89 mV/K. The temperature coefficients also depend on the ion implantation depths (Fig. 4b). For implanting ions into the depth of 3.4 μm at room temperature TCsemi of 2.03 mV/K is received, while for implanting into the depth of 3.8 μm the TCsemi increases to 3.13 mV/K. The insulator 15 thickness influences the temperature coefficients as well. Fig. 4c illustrates that the thinner the insulator layer the lower is the temperature coefficient. For example, for thickness of 40 nm the TCsemi is 1.78 mV/K while for 100 nm thick insulator the TCsemi increases to 2.05 mV/K. Fig. 4d illustrates the contribution of the electrolyte and the reference electrode to the thermal instability of the device. The thermal coefficients of the electrolyte and the reference electrode at three pH values were calculated and found to be 1.1 mV/K at pH 9 and 1.3 mV/K for pH 5.1. One technique for reduction of temperature dependency in ISFET measurements is to bias the device at the so called athermal point; a locus of minimum dIds/dT, where the drain current is not significantly thermally dependent. This effect is shown in Fig. 5 for p-BC-ISFET and n-BC-ISFET at two different pH values. It should be noted that the athermal point is not only dependent on the physico-geometric parameters of the device, but also on the pH value of the solution. It can also be seen from Fig. 5 that the threshold voltage of BC-ISFETs increases with pH; the threshold voltage of p-BC-ISFET increasing with rising temperature while the threshold voltage of n-BC-ISFET decreases with rising temperature. Fig. 6 shows the threshold voltages as a function of pH of p-BC-ISFET and n-BC-ISFET at three different temperatures. The average temperature coefficient of the p-BC-ISFET is +4.5 mV/oC while the n-BC-ISFET is -4.1 mV/oC. 16 Fig. 7 shows the transfer characteristics of the inverter at two pH values for three different temperatures. The two points of intersection of the curves at different temperatures at around VOUT = 0.2 V are athermal points. The impact of the site binding mismatch on the output voltage and the biasing current is demonstrated in Fig. 8. The ratio of silanol binding sites of p-BC-ISFET and n-BC-ISFET influence the output voltage and current of the inverter. It can be seen from Fig. 8 that varying the NsilP/ NsilN from 0.8 to 1.2 change the sensitivity of the device from 56.45 to 57.41 mV/pH. The current is also influenced by this change (of silanol ratio). In the symmetrical case when NsilP/ NsilN = 1, the current is constant in all pH range. Changing this ratio results in a non constant current, for example for NsilP/ NsilN the current decrease with pH while increasing this ratio beyond unity cause an increase in the inverter current. For inverter with non equal parameters of n-BC-ISFET and p-BC-ISFET (a2≠1), the output voltage will differ with silanol binding sites ratio in similar way to a device with equal parameters. Fig. 9 shows the output voltage of the circuit for a number of NsilP/ NsilN ratios. The sensitivity in the case of NsilP/ NsilN = 0.8 is 56.28 mV/pH and for NsilP/ NsilN = 1.2 the sensitivity is 57.46 mV/pH. While working in a non athermal point of the inverter as shown in Fig. 7, the output voltage is sensitive to pH changes caused by the temperature. Fig. 10 shows four graphs for output voltage of the inverter as a function of pH at three different 17 temperatures. In each graph the working point is different. The working voltage shown in Fig. 10a, 10 b and 10c are above the athermal point while Fig. 10d shows the output voltage of the inverter at the athermal point; at this point the three lines are almost parallel and for each Vout we see small changes at the pH value. In the three other figures we can see that the intersection point of all three curves increase with the applied voltage; for Vd of 0.3 V, the intersection point is at pH 8.5 (Fig. 10a), for Vd of 0.28 V the curve intersect at pH 7.5 and at Vd of 0.26 V this point decrease to pH 5.4. If the sensitivity didn’t depend on temperature the three output characteristics would lie on each other having zero temperature coefficients. Because it is not the case the temperature coefficients varies with pH. Discussion Semiconductor devices are sensitive to temperature variations. The model that has been developed and simulated points on the relative contribution of the semiconductor and the electrolyte of the temperature dependence of the BC-ISFET. In addition to the device behavior, the electrolyte characteristics, such as the pH value is also temperature dependent. In this paper we show that the output voltage of the ISFET is mainly influenced by the semiconductor temperature variations. In order to achieve better temperature immunity, we suggest a novel readout circuit. The circuit is based on an inverter configuration with two complementary BC-ISFETs. It is shown that in order to reduce the temperature coefficient to be as low as possible the devices should have thin insulator, shallow ion implantation and high dopant concentration in the conducting channel. For instance, p-BC-ISFET having tox=40 nm, Na=1017 [cm-3], Xi=3.4 µm gives 18 TCsemi ~ 1.75 [mV/K], which means that a temperature fluactuation of 10 K will shift the threshold voltage by 17.5 mV. Having a sensor with 58 mV/pH sensitivity will give a pH reading error of ~0.3 units, which is usually too high for most applications. Sensors with lower pH sensitivity (e.g. less than 58 mV/pH) will have even larger error. BC-ISFET has typically a higher temperature coeficffiecien (TC) than common enhancement ISFETs For example, the average temperature coefficient of a p-BC-ISFET is 4.5 mV/oC while the temperature coefficient of an enhancement ISFET with the same substrate and insulator parameters is 3 mV/oC. This means that the influence of temperature in BC-ISFETs is more detrimental to its pH-sensitivity than for enhancement ISFETs. In order to compensate the temperature sensitivity, a readout interface based on inverter configuration using two complementary BC-ISFETs has been developed and simulated (Fig. 3). The structure, as in a digital inverter, provides the same bias current flowing through both transistors, thus avoiding the bias current difference and minimizing the sizing mismatch, which are present in a differential pair technique. The circuit has no body effect, and features temperature compensation. Two different modes of the circuit are presented and we present the differences in their temperature compensation behaviors. The two different modes yield different behaviors regarding the temperature compensation feature. The first appears (Fig. 8) to be insensitive to pH variations caused by the temperature and its behavior is similar to the operation of a single device around the athermal point. The second mode (Fig. 10) is sensitive to pH fluctuations caused by the temperature and the error of the response is only due to the sensitivity’s temperature coefficient, which can not be eliminated. As a result, a maximum temperature coefficient is up to ± 0.3 mV/oC at pH=9 and pH=5 and 0 at pH=7. 19 The proposed circuit generates a siganl variation due to the individual sensors sensitivity mismatch, which is a result of a different number of the binding sites in pchannel and n-channel devices. We showed that both circuit implementations are relatively stable despite possible binding sites density mismatch. Deviation of up to 0.9 mV/pH from the sensitivity of the symmetrical case was introduced by a 20% mismatch of the silanol binding sites densities at the athermal point. A deviation of up to 0.6 mV/pH resulted for the second operation mode. According to equation 31, the sensitivity of the circuit is an average of individual sensitivities of the sensors. For equal sensitivities, when NsilP/NsilN=1, the ΔVOUT equals to 57.18 mV/pH. For the asymmetrical case the sensitivity ranges from 56.45 mV/pH to 57.41 mV/pH, resulting in deviation of less than 1% from the symmetrical case. It also should be noticed that the output voltage is shifted in either direction, which depends upon NsilP/NsilN relation and their absolute values. Greater density of binding sites results in positive shifts and negative ones otherwise. The current in the circuit is constant for the symmetrical case. When the sensitivities of the sensors are different, the current changes with pH. For the case NsilP<NsilN, the current falls with growing pH and rises otherwise. Although the current is not constant as it is supposed to be when employing the constant current mode of operation, its deviation from the average value is less than 0.5%, therefore, it can be neglected. The sensitivity in the case where NsilP/ NsilN = 0.8, is 56.28 mV/pH. However, in the case where the ratio was the opposite, e.g. NsilN / NsilP = 0.8, the calculated sensitivity is 56.61 mV/pH. This result supports the claim that the p-channel sensor is dominant in the determination of the final circuit. Therefore, the circuit has larger 20 degradation of sensitivity (0.9 mV/pH) from the symmetrical case (NsilP/ NsilN = 1) than the one shown in Fig. 8 for a 2 1 (equal fabrication parameters of the two transistors). Another reason for binding sites variations can be due to organic molecules bonded to the gate insulator for biosensing purposes. These organic monolayers have two main functions; one as a covalent binding layer which enables biological molecules attachment. This layer usually contains amine or carboxyl groups. The second role of the organic layer originates from the ability to control the surface functionality. In this manner, fabrication of an array of sensors in which an individual sensor has different functionality will enable to create a differential sensor with a built in reference. Assume a dual sensor composed of two ISFETs, one with an active surface that enables binding bio-molecules (e.g., containing amine groups) while the other is passive and does not enable to interact with the biological species in the solution (e.g., fluorine or methyl groups).This kind of sensor will have a reference inside which will minimize readout errors due to environmental changes as pH or temperature. However, organic monolayers assembled on the gate insulator usually form a non uniform layer. The defects and domains in the monolayer may result in a different number of silanol sites of both ISFETs. Moreover, monolayers with different functional groups have different reaction coefficients and different number of donor and acceptors sites; this affects directly the induced charge at the lectrolyte/insulator interface and, therefore, affects the threshold voltage of the transistors. Conclusions 21 A physical model of BC-ISFET including second-order effects has been presented in this work. The influence of different chemical and semiconductor related parameters on BCISFET’s sensitivity in Phosphate Buffered Saline solution has been studied using MATLAB simulations. The temperature effect on the operation of the buried channel ISFET is shown and an electrical inverter is suggested to minimize temperature influence on the output signal. It was shown that the number of binding sites is a major factor influencing the sensitivity of the inverter. It also affects the threshold voltage of the device. Higher densities of the binding sites result in higher threshold voltages. 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(d) Contribution of the chemical part of the system to the threshold voltage and the associated temperature coefficient (TCchem.). Fig. 5: Simulation results of Ids/Vgs curves for two pH values, showing the athermal points of (a) n-BC-ISFET and (b) p-BC-ISFET at different temperatures. Fig. 6: Threshold voltage vs. pH of (a) n-BC-ISFET and (b) p-BC-ISFET at three different temperatures. Fig. 7: BC-ISFET inverter characteristics at two pH values at different temperatures where VS=0.4 V. 25 Fig. 8: (a) Output voltage and (b) Current of BC-ISFET inverter circuit for different ratios of silanol binding site densities when fabrication parameter of the two transistors are equal ( a 2 1 ), VDS=0.2V. Fig. 9: Output voltage for different ratios of silanol binding sites densities where a2=0.56. Fig. 10: Output voltage of BC-ISFET inverter configuration readout circuit with minimum temperature dependence at three temperatures for gate bias of (a)0.3 V, (b)0.28 V, (c)0.26 V and (d) 0.2 V. 26