Exploration of Ion Sensitive Field-Effect Transistor With Dielectric Properties

Environmental changes and increased virus effects in COVID-19 like the situation is forcing the design and researchers to develop highly sensitive, low power and low cost mean to detect the presence of biomolecules of different shapes, sizes, and their effects on the human being. Ion-sensitive eld-effect transistor (IS-FET) is a biological sensor based on the architecture of metal oxide semiconductor eld-effect transistor (MOS-FET). The gate terminal is replaced with a hollow space lled by electrolyte solution and reference electrode at the external surface. The biomolecular enzyme in contact with membrane enters in solution induce net DC potential, alter the oxide surface. The alteration of surface puts variation in threshold voltage and maps on the deection of drain current. ISFET measures the concentration of charged particles (ions) in the solution; variation into ion concentration produces deection in the drain current. In this work numerical simulation of ISFET is performed with ENBIOS-2D Lab at Nanohub platform with dielectric SiO 2 , Al 2 O 3 , HfO 2 with NaCl and KCl in solution. Channel resistance and capacitance with 3-different electric shows a large variation of capacitance, result in threshold voltage i.e. 318.2 mV with SiO 2 and 319.2 mV with Al 2 O 3 .


Introduction
Chemical sensor research based on Ion-sensitive eld-effect transistor (ISFET) is dynamic in the area of environmental monitoring application, biomedical molecule, analytical chemistry, and pharmaceutical testing since invented by P. Bergveld [1] in 1972. It works as a biological electronics interface; architecture is similar to the existing metal-oxide eld-effect transistor (MOSFET), the only difference lies in terms of gate terminal. In MOSFET gate electrodes are in contact with the oxide dielectric layer while in ISFET the oxide dielectric is in contact with the reference electrode via electrolyte solution [2]. ISFET is 3 terminal devices; source, drain, gate presented in Fig. 1 consist of a combination of biological elements and a semiconducting transducer layer [3]. Stable reference electrodes are placed to set the constant gate surface potential. The conduction layer is similar to the conventional eld-effect transistor; the functionality of the dielectric layer is understood as isolation of channel and coupling of bimolecular charges to the channel. A bio-functionalized layer exhibits an immobilized bimolecular charge known as a receptor on the top of the dielectric [4].
Sensing of biological signals with FET devices drew attention due to its excellent sensing properties and effective cost. Conventional FET devices establish the ow of current between sources and drain terminal under the in uence of electric led produces by potential applied at 3rd gate terminal, whereas in ISFET gate electrode are in the contact of the electrolytic solution. The gate surface must bio-functionalized with receptor molecule that gets capture into the FET gate surface result in the variation of its surface potential. Due to the variation of charge, it affects the measurable drain to source current [5]. It senses the biomedical signal and integrates the amplifying device on the chip itself. The sensing of bio-molecular detection is based on NMOS, a biotin-streptavidin complex chosen for the modeling due to puri cation and delectability [6]. The presence of ion particles creates DC potential in the solution. Biasing of ISFET induces, energy barrier, doesn't remain the constant between Fermi level and oxide breakdown, the distinction between valance electron level of the conduction particle species in the electrolyte and oxide conduction band.
The ability of ISFET to sense the living cell attracts the researcher to reads the biological information [7], majorly nd application in drug screening, sensing the biochemical compound, and study of neural network. It ensures pH and other electrolyte solutions, exposed to the dielectric to the electrolyte acts as a biological FET (BioFET) based sensor. The biological sensor eld-effect transistor is a combination of sensitive biological recognition elements and is the FET that can detect the antigen in the body and tumor markers. BioFET measures the change in surface potential induced by binding of the molecule when the bimolecular binds with the gate terminal (a dielectric material). A pH-sensitive oxide layer in contact with electrolyte solution under biased condition, variation in pH value is detected which is measure by variation in drain current [8]. DC Current in electrolyte-oxide-semiconductor (EOS) is accompanied by electrolysis which is visualized by the production of gas at the electrode. Higher drain to source potential V DS holes repeal from source terminal, create a conduction channel of the hole. The charged particle directed towards gate oxide (x-direction) potential varies with distance concerning the reference electrode. The electrical readout of ISFET is the drain to source voltage proportional to the pH concentration of the electrolyte as presented in [9,10]. A biological enzyme enters the solution reacts with salt and frees the ion, electrons, and holes. Hydrogen ion concentration controls the drain to source current, pH solution contains H + ion. A higher concentration of H + ion has a low pH value and vice versa. Positive charge ions produce electrical potential by way to diffuse through the membrane at oxide layer, tends to except H + ion requires additional gate voltage to maintain constant threshold voltage to create a channel between source to drain. The selectivity and sensitivity of ISFET highly depend on the selection of gate and sensitivity of the surface of dielectric material [11][12][13]. I DS depends on the potential difference over gate oxide, in uenced by the oxide-electrolyte solution.
In this work, the dielectric layer experimented with different materials SiN 4 , Al 2 O 3 , Ta 2 O 5 , SiO 2 which acts independently to H + ions. The biological analytes in the solution decrease the binding and enable the charge transfer to the surface of the transducer chemically or electrostatic interaction. During the interaction between membrane and target variation in the oxide surface seen which turn in the change in conductivity of channel, by measuring the change the binding of the analyte can be detected [14]. Section 2 discusses the surface potential induces by the reference electrode and gate oxide. Simulation results obtained with nanohub tool included in Sect. 3, Sect. 4 read out the variation in threshold voltage (V th ) nally concluded in Sect. 5.

Isfet As Sensor
ISFET based biosensors nd commonly for the early detection of various diseases since molecules transmit electrical charges rapidly. The existing CMOS fabrication process offers the advantage of miniaturizing and concurrent sensing. Different biological analytes have experimented with for the detection of viruses including COVID-19, In uenza, and Hepatitis-B, etc, besides it also uses for designing nucleic acid sensors depends on DNA hybridization [15]. The advantage of the ISFET sensor emerges in speed, sensitivity, speci city which is the primary requirement of COVID-19 detection presented in [16].
Graphene-based FET biosensors can detect surroundings changes in their surface and provide an optimal sensing environment for low noise detection. The electrolyte solution used to cover is phosphate-buffered saline (PBS, pH = 7.4) to maintain an e cient gate electrode. Based on the charge in aqueous solution in surface potential and their effect on the electrical characteristics can detect SARS-CoV-2 spike on the surface V-I characteristics over ranges of -0.1 to + 0.1 V before and after attachment of the antibody, after immobilization of antibody on the surface the slope (dI/dV) decreased, the difference in slope presented the introduction of SARD-CoV2 spike antibody.

Reference Electrode
FET structures of the biosensor are equivalent to insulated gate FET (IGFET) or ISFET. In IGFET the gate terminal is detached from the source and channel terminal while in an ISFET gate terminal is supplanted by the particle-speci c lm, reference electrode, and electrolyte. In ISFET the channel appeared due to an electrochemical effect [17]. In MOSFET capacitive effect is due to the dielectric layer while in ISFET capacitive effect due to the cumulative effect of the dielectric layer and capacitance of the electrical double layer (EDL). The EDL arises due to the distribution of the ion in solutions near the solid-liquid interfacing surface and exerts a capacitance known as electrical double layer capacitance (EDLC) [18]. EDLC can calculate by applying a potential in the liquid, the polarity of EDL can change by bias voltage in the solution. ON and the OFF state of ISFET can relate as presence and absence of charge carrier in the channel presented in Fig. 2. A reference electrode usually (Ag or AgCl) used to apply the bias voltage in the solution. Charge molecule on the surface and binding of analyte molecules produces a change in the surface charge result in a change in the effective gate voltage needed to turn ISFET ON/OFF. The current ow not only due to the charges of bimolecular interacting on gate electrode but also sensitive to pH of uid, different ions, enzyme reaction [19] Biological sensitive FET is highly sensitive to select the biomedical or chemical analyte due to the biorecognition layer at the surface. The performance of a biosensor depends on the selection of a biorecognition layer. These layers provide speci c interaction with molecules, binding, and charge transfer. The electrical detection of biomolecules in the solution follows a different strategy. A small charged molecule in a low ionic solution needed potentiometric readout. pH-sensitive array-based Biosensor, remove the metal gate from top and passivation layer is deposited. This layer creates additional capacitance in series; which limits the sensitivity [20] ISFET based sensing application requires a stable reference electrode, and indistinguishable from a change in detectable chemical potential. Ag/AgCl element in the membrane covers within ± 0.5 mV in 0.1 M in the mixture of NaCl or KCl solution. RC model at the electrode reveals the ion to electron conduction principle at the reference electrode by redox reaction [20].
Redox sensitive material at the reference electrodes measures capacitance C while current i ow through electrode voltage v, a small resistance exhibit that shifts the potential, described miniaturization of reference electrode increase the resistance and decrease in capacitance [21].
The passivation layer for sensing creates variation in the threshold due to charge trap in the layer [21] The resulting sensors are highly successful in pH measurement. The reduction in threshold voltage is measured by Eq. (1) Where V CHEMICAL is the voltage induced by electrochemical process, E i is chemical constant, F is Faraday constant, T is the temperature in kelvin, R is gas constant, a i is the activity of ion, and ηis ion charge [22] 2.2Oxide surface potential For 30 years several fabrication methodologies for ISFET sensors have been proposed with different materials. The processing equipment of ISFET fabrication is common with integrated technology (IC) technologies fabrication. Fabrication begins with, < 100 > p-type semiconductor as substrate and heavily doped by n-type semiconductor creates source and drain terminal. The doping level ensures a low leakage current. In this work, ISFET has experimented with materials like SiO 2   Bimolecular enzyme touches the membrane reacts with salt in the solution and induces the charged particle. Movements of charged particle towards gate oxide in the z-direction (at x = 0 nm, center of the silicon lm, and at z = 24 nm, i.e., one nm above the Si-Dielectric interface) presented in Fig. 4. It is observed that a negative peak occurs due to the charge built up near the site binding at the dielectric and electrolyte interface. The concentration of ions with V FG =0 V the Na + ion is higher than Cl − concentration,  for SiO 2 , Al 2 O 3, and HfO 2 respectively. The potential tend to decrease with the upward Z-axis; can be approximated to zero afterward 52 nm from oxide electrolyte interface. As enzymes in contact of membrane react with electrolyte solution free the charged particle, when their concentration reaches the signi cant value of 6.023*10 23 /m 3 at a distance of 52 nm; DC potential induces 0.157 mV. DC potential along X-axis (z-direction) shown in Fig. 6(b) is minimum at the center of oxide, reaches the maximum value to both sides. DC voltage rises exponentially till z = 100 nm; reaches a maximum value of 0.575V The variation in resistance (solid line) and capacitance (dashed line) in the channel with different dielectric is presented in Fig. 7

Conclusion
In this work, the detailed analysis of ISFET structure with the involvement of different dielectric as a gate oxide in an electrolyte solution with NaCl and KCl salt has been presented. Simulation result obtained with ENBIOS-2D Lab of Nanohub computes maximum variation is found with high K dielectric at the gate terminal. DC potential induced solution towards gate oxide is a maximum of 0.069 V for SiO 2 dielectric and 0.061736 V with HfO 2 dielectric. For the frequency range of 1KHz to 1GHz, the channel resistance is directly related to the K value and channel capacitance is inversely related to the K value. The high value of de ection current shows that HfO 2 offers low resistance in comparison to SiO 2 and Al 2 O 3 . The projected analysis can be extended to other available FET-based sensors such as multi-gate MOSFET or TFET architectures.

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The simulation work has been carried out using open-source online simulator nanohub.
Authors' contributions (optional): NA The performance evaluation of Bio-FET has been covered in this work.

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We are ready for publication with your journal.  Concentration of Charged particle in NaCl Solution