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• Fabrication of ISFETs. • Experimental analysis of ISFET for potassium chloride (KCl) sensing. • Sensitivity analysis for measurement methods, with one and two platinum electrodes. This work presents the fabrication and electrical characterization of the Ion Sensitive Field Effect Transistor (ISFET) exposed to potassium chloride (KCl) solutions. The focus of the study is to compare two measurements methods and verify the effects of these methods in the device threshold voltage (V TH) sensitivity to the different KCl concentrations. First, a reference electrode (a platinum needle) is placed in the sample solution over the gate area of the device, demonstrating that the threshold voltage decreases with the increase of the KCl concentration. The method shows a sensitivity of 10.44 mV/mM for the low KCl concentration range (0 to 10 mM) and 0.5 mV/mM for the higher KCl concentration range (10 to 100 mM). The second method involves inserting a second platinum electrode into the solution on the field oxide. This method proposes the KCl electrolysis to increase the selectivity for potassium ions. The result allows the next steps for potassium sensing biosensor application with selective membranes. [ABSTRACT FROM AUTHOR]

This paper describes a novel design of ISFET, which uses a hafnium oxide-coated aluminum pad surface as a floating/extended gate. The design was realized using standard CMOS technology followed by BEOL post treatment. The ISFET was designed to operate in subthreshold mode and has subthreshold slope of 108 mV/dec, pH sensitivity of 55 mV/pH and temporal stability 0.008 mV/min. Based on the ISFET, an enzymatic biosensor for detection of phenols in real samples was demonstrated. The reported design allows to significantly improve the internal characteristics of ISFET, leading to predictable high-performance biosensors formed on a basis of standard CMOS-technology. [ABSTRACT FROM AUTHOR]

Here, we explicitly define a half-cell reaction approach for pH calculation using the electrode couple comprised of the solid-state chloride ion-selective electrode (Cl-ISE) as the reference electrode and the hydrogen ion-selective ion-sensitive field effect transistor (ISFET) of the Honeywell Durafet as the hydrogen ion H + -sensitive measuring or working electrode. This new approach splits and isolates the independent responses of the Cl-ISE to the chloride ion Cl − (and salinity) and the ISFET to H + (and pH), and calculates pH directly on the total scale pH total EXT in molinity (mol (kg-soln)−1) concentration units. We further apply and compare pH total EXT calculated using the half-cell and the existing complete cell reaction (defined by Martz et al. (2010)) approaches using measurements from two SeapHOx sensors deployed in a test tank. Salinity (on the Practical Salinity Scale) and pH oscillated between 1 and 31 and 6.9 and 8.1, respectively, over a six-day period. In contrast to established Sensor Best Practices, we employ a new calibration method where the calibration of raw pH sensor timeseries are split out as needed according to salinity. When doing this, pH total EXT had root-mean squared errors ranging between ±0.0026 and ±0.0168 pH calculated using both reaction approaches relative to pH total of the discrete bottle samples pH total disc. Our results further demonstrate the rapid response of the Cl-ISE reference to variable salinity with changes up to ±12 (30 min)−1. Final calculated pH total EXT were ≤±0.012 pH when compared to pH total disc following salinity dilution or concentration. These results are notably in contrast to those of the few in situ field deployments over similar environmental conditions that demonstrated pH total EXT calculated using the Cl-ISE as the reference electrode had larger uncertainty in nearshore waters. Therefore, additional work beyond the correction of variable temperature and salinity conditions in pH calculation using the Cl-ISE is needed to examine the effects of other external stimuli on in situ electrode response. Furthermore, whereas past work has focused on in situ reference electrode response, greater scrutiny of the ISFET as the H + -sensitive measuring electrode for pH measurement in natural waters is also needed. • Electrode responses are split out and isolated using half reactions. • A new approach for pH calculation using half reactions is explicitly defined. • pH calculation uses single ion activity coefficients for the chloride and hydrogen ions. • This new pH calculation approach is optimized for salinities between 0.105 and 35. • pH can now be calculated directly on the total scale in molinity (mol (kg soln)−1). [ABSTRACT FROM AUTHOR]

Accurate diagnose of a disease in the early stage is critical to treat the disease properly. To this end, a multitude of biosensors with advanced technologies have been developed to detect the number of biomolecules precisely. In this work, we propose a method for extracting the Stern layer capacitance (C stern) using the experimental data of silicon nanowire ion-sensitive field-effect transistors (ISFETs) to help improve the accurate detection of target molecules. The proposed method was applied to both pH and virus sensing scheme, and the C stern value of pH and a virus were extracted as 32 and 26 μF/cm2, respectively. These findings indicated that the extracted C stern was affected by the size of the ion and protein, which also was verified by a computer-aided simulation. These insights would be useful in the development of charge-based ISFET biosensors. [ABSTRACT FROM AUTHOR]

In this work, we have investigated, both theoretically and experimentally, the analog study of the ion-sensitive field effect transistor (ISFET) and the circuit design for pH sensing. The gate electrode work function engineered on ISFET has been rigorously investigated for the analog/RF applications by using the Cogenda Visual TCAD tool. Based on its I–V characteristics, we may deduce that molybdenum, with a work function of 4.75 eV, has a larger threshold voltage, switching ratio (1 0 4 ) and lower leakage current (1 0 − 3 ) than aluminum at 300 K. In addition, we experimentally investigated the enhancement in pH sensing. ISFET display instability, often referred to as drift, in the form of a gradual, monotonic, temporal increase in the device's threshold voltage. The validation of the observations was done by increasing the value of the pH as follows: 4.67, 5.9, 7.5, 8.57, and 9.3 which was checked by pH meter. • This article studies the analog properties and switching performance of ISFET for different work functions by TCAD software. • The article also studies the experimental circuit design for various pH values as follows: 4.67, 5.9, 7.5, 8.57, 9.3. • Molybdenum (Mo) as a gate electrode enhances the switching speed, and lowers the leakage current rather than aluminum, chromium. • The sensitivity and reference voltage is improved at higher pH. [ABSTRACT FROM AUTHOR]

• CMOS ISFETs passivation layers plasma etching method for minimal surface roughness. • Identification of spatial distribution of trapped charge in CMOS ISFET passivation. • Performance improvement of CMOS ISFETs including 731% increase in sensitivity. In this work, we investigate the impact of successively removing the passivation layers of ISFET sensors implemented in a standard CMOS process to improve sensing performance. Reactive ion etching is used as a post-processing technique of the CMOS chips for uniform and accurate etching. The removal of the passivation layers addresses common issues with commercial implementation of ISFET sensors, including pH sensitivity, capacitive attenuation, trapped charge, drift and noise. The process for removing the three standard layers (polyimide, Si 3 N 4 and SiO 2) is tailored to minimise the surface roughness of the sensing layer throughout an array of more than 4000 ISFET sensors. By careful calibration of the plasma recipe we perform material-wise etch steps at the top and middle of the nitride layer and top of the oxide layer. The characterisation of the ISFET array proves that the location of the trapped charge in the passivation layers is mainly at the interface of the layers. Etching to the top of the oxide layer is shown to induce an improvement of 80% in the offset range throughout the array and an increase in SNR of almost 40 dB compared to the non-processed configuration. The performance enhancement demonstrates the benefit of a controlled industry-standard etch process on CMOS ISFET array system-on-chips. [ABSTRACT FROM AUTHOR]

• Encapsulating graphene with parylene improves ion sensing performance. • Quiet, low-noise amplification with large-area graphene leads to better precision. • Potassium detection limit is three orders better than state-of-the-art. • Sensors exhibit remarkable stability and reproducibility over a five-month period. We demonstrate large-area graphene based ion sensitive field effect transistors (ISFETs) with potassium ionophore sensing layers. Graphene ISFETs encapsulated with an ultra-thin hydrophobic layer, parylene C, and active areas ∼0.4 cm2 are characterized by an rms current noise as low as 5 nA in a 60 Hz electrical bandwidth, field effect mobilities up to 5000 cm2 V−1 s−1 and quantum capacitance limited coupling. Real-time sensing of K+ was achieved with a detection limit of 10−9 M K+, equivalent to 39 ng/L, and a resolution of ∼2 ×10−3 log [K+]. The ISFETs exhibit reversibility under spiking experiments and long term stability with limited drift over a course of five months. The cross-sensitivity has been measured to be 2.5 mV/decade for Na+, 4.2 mV/decade for Ca2+, 1.5 mV/decade for Mg2+ and 9.0 mV/decade for NH 4 +. Experiments with a variety of specimens, including beverages and blood, confirm the suitability of graphene ISFETs for K+ sensing in fluids with multiple solutes. The graphene ISFET design can be extended to sensing of other ionic species by substitution of alternative ionophores within the sensing membrane. [ABSTRACT FROM AUTHOR]

Abstract The importance of specific and label-free detection of proteins via antigen-antibody interactions for the development of point-of-care testing devices has greatly influenced the search for a more accessible, sensitive, low cost and robust sensors. The vision of silicon field-effect transistor (FET)-based sensors has been an attractive venue for addressing the challenge as it potentially offers a natural path to incorporate sensors with the existing mature Complementary Metal Oxide Semiconductor (CMOS) industry; this provides a stable and reliable technology, low cost for potential disposable devices, the potential for extreme minituarization, low electronic noise levels, etc. In the current review we focus on silicon-based immunological FET (ImmunoFET) for specific and label-free sensing of proteins through antigen-antibody interactions that can potentially be incorporated into the CMOS industry; hence, immunoFETs based on nano devices (nanowire, nanobelts, carbon nanotube, etc.) are not treated here. The first part of the review provides an overview of immunoFET principles of operation and challenges involved with the realization of such devices (i.e. e.g. Debye length, surface functionalization, noise, etc.). In the second part we provide an overview of the state-of-the-art silicon-based immunoFET structures and novelty, principles of operation and sensing performance reported to date. Highlights • Specific and label-free immunosensing via protein-protein interactions using silicon FETs are discussed. • This review illustrates the operation principle of silicon based immunoFETs along with the design concerns and challenges. • Different device architectures proposed to overcome the design challenges of silicon-based immunoFETs are reviewed. [ABSTRACT FROM AUTHOR]

Abstract A new bioelectronic nose based on a field effect transistor coupled with an aptamer as the sensing element was developed. The gas-to-liquid extraction interface required for appropriate aptamer function was integrated into standard CMOS technology. It was developed with the use of a sacrificial aluminium etching technique combined with surface modifications by silanes for wettability control. As a proof of concept, aptamer Van74 for vanillin was immobilized on the sensitive surface of the ISFET. The developed microsystem can selectively detect vanillin vapor in a concentration range from 2.7 ppt to 0.3 ppm, with a detection limit of 2.7 ppt. The sensor was able to detect vanillin in a gas sample obtained from roasted coffee beans. This outcome provides a foundation for developing a new generation of bioelectronic noses for the detection and discrimination of volatile compounds. Highlights • A novel bioelectronic nose based on the aptamer and ISFET was introduced. • Fabrication of a gas-to-liquid extraction interface was integrated in standard CMOS-technology. • The fabricated bioelectronic nose allowed selective detection of vanillin in coffee aroma. [ABSTRACT FROM AUTHOR]

• TCAD simulation of liquid-gate graphene field effect transistor. • Tuned user-defined materials to include the electrolyte and monolayer graphene effect. • Anchored antibodies in the surface of the sensor modeled as charged boxes. • Antibody-Antigen binding event modifies the charge trapped at the surface of the sensor. • Response of the sensor measured as the drift of the minimum current point of the current–voltage characteristic. We used a commercial TCAD simulator for the study of liquid-gate Graphene FETs as antibody-based sensors. To model the graphene layer, a zero-bandgap semiconductor with a linear density of states relationship in both the conduction and valence bands near the edge of the bands was adopted. The electrolyte which forms the liquid gate was also modeled as a semiconductor with tuned parameters to reproduce the behavior of a dilute PhosphateBuffer Saline (PBS) solution with pH = 7.4. Antibodies are anchored to the graphene surface and their effect is simulated with a charged cube box with a size similar to the one of the IgG antibody and a charge concentration similar to the charge usually carried by an anibody. The binding of the antibody with the antigen protein (Ab-Pr) complex is also represented in the simulator with a charged box carrying a different charge. We have calculated the I D -V FG curves for different numbers of antibodies anchored to the surface of the graphene and analyzed the behavior of the sensor as a function of the number of antibody-protein complexes. [ABSTRACT FROM AUTHOR]

An integrated sensor chip with silicon nanowire ion-sensitive field-effect transistors for simultaneous and selective detection of both molecular and elemental ions in a single sample solution is demonstrated. The sensing selectivity is realized by functionalizing the sensor surface with tailor-made mixed-matrix membranes (MMM) incorporated with specific ionophores for the target ions. A biomimetic container molecule, named metal-organic supercontainer (MOSC), is selected as the ionophore for detection of methylene blue (MB + ), a molecular ion, while a commercially available Na-ionophore is used for Na + , an elemental ion. The sensors show a near-Nernstian response with 56.4 ± 1.8 mV/dec down to a concentration limit of ∼1 μM for MB + and 57.9 ± 0.7 mV/dec down to ∼60 μM for Na + , both with excellent reproducibility. Extensive control experiments on the MB + sensor lead to identification of the critical role of the MOSC molecules in achieving a stable and reproducible potentiometric response. Moreover, the MB + -specific sensor shows remarkable selectivity against common interfering elemental ions in physiological samples, e.g. , H + , Na + , and K + . Although the Na + -specific sensor is currently characterized by insufficient immunity to the interference by MB + , the root cause is identified and remedies generally applicable for hydrophobic molecular ions are discussed. River water experiments are also conducted to prove the efficacy of our sensors. [ABSTRACT FROM AUTHOR]

Here we report an electrochemical immunoassay platform called Proton-ELISA (H-ELISA) for the detection of bioanalytes. H-ELISA uniquely utilizes protons as an immunoassay detection medium, generated by the enzyme glucose oxidase (GOx) coupled with Fenton's reagent in a proton amplification reaction cascade that results in a highly amplified signal. A proton-sensitive dual-gated ion-sensitive field effect transistor (DG-ISFET) sensor was also developed for sensitive and accurate detection of the proton signal in H-ELISA. The DG-ISFET sensor comprises of a 128 × 128 array of 16,384 sensing transistors each with an individually addressable back gate to allow for a very high signal throughput and improved accuracy. We then demonstrated that the platform could detect C-reactive protein and immunoglobulin E down to concentrations of 12.5 and 125 pg/mL, respectively. We further showed that the platform is compatible with complex biological sample conditions such as human serum, suggesting that the platform is sufficiently robust for potential diagnostic applications. [ABSTRACT FROM AUTHOR]

We describe the pH dependence of the electron mobility as a function of various structural and electrolyte factors for unfunctionalised AlGaN/GaN-based chemical sensors. The charge distribution across the sensor-electrolyte system is calculated self-consistently and the dependence of the Hall mobility of the two-dimensional electron gas on different scattering mechanisms is studied. Our calculations show that the pH of the electrolyte has a significant effect on the mobility and consequently the conductivity of the 2DEG channel electrons. A wide range of structures is examined to describe the correlation between the sensitivity and channel electron density. It is shown that the change of mobility with pH is a strong function of the structure of the sensor (AlGaN, GaN-cap and oxide-layer thicknesses), while it is almost independent of the ionic strength of the electrolyte. The observed dependence of the Hall-mobility to the thickness of AlGaN-barrier, GaN-cap and oxide layer can explain the discrepancy in the behaviour of the Hall-mobility, as reported by different groups. [ABSTRACT FROM AUTHOR]

Consider advances are being made to develop new technologies capable of fast in-situ tracing of agricultural toxins. In this work, we reported a simple carbaryl sensor with very high sensitivity using graphene interdigitated ion selective field effect transistor (ISFET). The graphene films were first prepared on polycrystalline copper foil by a low-pressure chemical vapor deposition method, and then transferred onto the interdigitated electrodes of ISFETs by a chemical etching technique. The biorecognition is based on the enzymatic inhibition of carbaryl towards urease. As expected, the weaker enzymatic activity of urease in addition of carbaryl would result in the weaker current response. It was demonstrated that the interdigitated ISFET sensor could achieve high sensitivity to detect carbaryl as low as 10 −8  μg mL −1 and the current response of the device showed a good linearity against the logarithm of carbaryl concentration C carbaryl with a regression equation ΔI ds  = −0.4 − 0.6 logC carbaryl (mA) (R 2  = 0.99) in the concentration range from 2.58 × 10 −7 to 2.58 × 10 −2  μg mL −1 . In conlusion, such convenient graphene-based ISFET configuration could be advantageously extended for on-line screening of other pesticide and herbicide agents. [ABSTRACT FROM AUTHOR]

The use of high-k dielectric materials for the gate insulator of nanoscale Ion-Sensitive Field-Effect Transistor (ISFET) has been demonstrated to generally improve the ISFET performance. High-k gate insulator reduces the gate leakage current and increases the gate capacitance, which lead to higher trans -conductance and higher current sensitivity. The best high-k material for ISFET sensors is not simply the material of highest dielectric constant because high-k ISFET performance depends on many conflicting factors such as dissociation properties with electrolytes and linearity of voltage/current variation with pH change. In this work, a comparative simulation study is presented for six high-k gate insulators (Si 3 N 4 , Al 2 O 3 , ZrO 2 , Ta 2 O 5 , HfO 2 , and TiO 2 ), along with SiO 2 for comparison, for nanoscale ISFET sensors, comparing their sensitivity and linearity. The simulation tool used (NIST) is based on the numerical solution of nanoscale ballistic MOSFET equations along with Gouy-Chapman-Stern model equations. The study presents a guideline for the determination of the optimum insulator material and insulator thickness used for nanoscale ISFETs. The study included single-layer as well as double–layer insulators in which two layers of different dielectric materials are used. [ABSTRACT FROM AUTHOR]

A simple and rapid Chlorella sp. surface expressed alkaline phosphatase (AP-algae) biosensor modified with flower shaped ZnO nanoparticles for the determination of chlorpyrifos in an aqueous medium was developed. The detection principle was based on the inhibition of AP-algae in presence of chlorpyrifos. Enzyme would dephosphorylate the phosphate monoester of substrate 2-phospho- l -ascorbic acid to release l -ascorbic acid, which was monitored using voltammetric and ISFET techniques. The presence of pesticide would inhibit AP-algae enzyme activity and hence the current magnitude decreases. The decrease in current is quantitative in nature and used for determination of concentration of the pesticide. Flower shape ZnO nanoparticles not only provide surface for adsorption of AP-algae for better immobilization but also increases electron-transfer kinetics and sensitivity of the biosensor. The voltammetric and ISFET methods could measure chlorpyrifos in the linear concentration range from 10 −9 M to 10 −1 M and 10 −10 M to 10 −3 M, respectively, with nil interference from triazophos, malathion, acephate and some metal ions. Application aspects of the proposed biosensor were demonstrated using extracted soil samples and showed excellent reproducibility and reliability. [ABSTRACT FROM AUTHOR]

pH measuring and monitoring is fundamental to understand or control many chemical processes in biological, industrial or environmental fields. Potentiometric measurements by a glass electrode is the most common method to measure pH, although single-use paper strips are also widely used. Other methods include the use of hydrogen, quinhydron, and antimony electrodes, the imaging using pH-sensitive indicators such as dyes or proteins, and the use of ion-selective field effect transistor (ISFET). Due to the chemical reactivity of both sides of its 2D structure, nanometer thickness, high electron mobility, high reactivity to oxygen groups such as OH − , and ultrafast optical response, graphene has the potential to be used for the fabrication of nanoscale, wide-range, high-sensitivity and flexible pH sensors. This review describes how graphene, graphene oxide and reduced graphene oxide can be used to fabricate pH-sensitive devices (e.g. solution-gated FETs, solid-gate FETs, electrochemical sensors, and pH-sensitive quantum dots). The various configurations are reported along with the advantages and current limitations. [ABSTRACT FROM AUTHOR]

In this study, we investigate the effect of rising time (T R ) of liquid gate bias (V LG ) on transient responses in pH sensors based on Si nanowire ion-sensitive field-effect transistors (ISFETs). As T R becomes shorter and pH values decrease, the ISFET current takes a longer time to saturate to the pH-dependent steady-state value. By correlating V LG with the internal gate-to-source voltage of the ISFET, we found that this effect occurs when the drift/diffusion of mobile ions in analytes in response to V LG is delayed. This gives us useful insight on the design of ISFET-based point-of-care circuits and systems, particularly with respect to determining an appropriate rising time for the liquid gate bias. [ABSTRACT FROM AUTHOR]

The seminal importance of detecting ions and molecules for point-of-care tests has driven the search for more sensitive, specific, and robust sensors. Electronic detection holds promise for future miniaturized in-situ applications and can be integrated into existing electronic manufacturing processes and technology. The resulting small devices will be inherently well suited for multiplexed and parallel detection. In this review, different field-effect transistor (FET) structures and detection principles are discussed, including label-free and indirect detection mechanisms. The fundamental detection principle governing every potentiometric sensor is introduced, and different state-of-the-art FET sensor structures are reviewed. This is followed by an analysis of electrolyte interfaces and their influence on sensor operation. Finally, the fundamentals of different detection mechanisms are reviewed and some detection schemes are discussed. In the conclusion, current commercial efforts are briefly considered. [ABSTRACT FROM AUTHOR]

A series of novel calixarene-based tubes comprising different numbers of silatrane anchoring groups was synthesized. For the first time, a self-assembled monolayer (SAM) derived from calixtubes was formed on a SiO 2 surface. The formation of the SAM was confirmed by X-ray photoelectron spectroscopy, scanning electron microscopy-energy dispersive X-ray analysis, and contact angle measurements. Modification of the sensitive surface of a conventional ion-selective field effect transistor (ISFET) with the afforded SAM resulted in the production of a KI-sensitive sensor. This sensor selectively determined KI compare to different alkali metal iodides: NaI, RbI, CsI; also investigation of different potassium salts (acetate, iodide, nitrate, chloride, dihydrophosphate, perchlorate) showed the highest response to KI. This sensor was successfully employed to determine the presence of KI in artificial saliva with a limit of detection of ~3 × 10 −8 М. In addition, it was found that the detection limit of the sensor could be increased by combining the sensor with a microfluidic system. Due to the obtained sensor sensitivity and its ability to detect KI in artificial saliva, we could conclude that this sensor shows great potential for application in the determination of KI in different media, such as the human body and in biological liquids, such as saliva or urine. [ABSTRACT FROM AUTHOR]

This paper reports a high-performance double-gate zinc-oxide thin-film ion-sensitive field-effect transistor (DG-ZnO-ISFET) for pH sensing applications. The sensing mechanism of DG-ZnO-ISFET and a simulation model for pH sensing analysis are demonstrated herein. Various aspects of the device are elucidated through the study of channel conductance, electron density, energy band, and surface-potential profiles. The DG-ZnO-ISFETs enhance minor surface potential variations by capacitive coupling across the dielectrics of the top and bottom gates. Further, it operates by altering the bottom-gate voltage (V B G), obviating the need for a reference electrode system. The device depicts enhanced voltage sensitivity of 205.57 mV/pH , which is substantially 3.48 × greater than the Nernst limit sensitivity. In addition, the DG-ZnO-ISFET renders a maximum current sensitivity of 10.82 mA/mm.pH at V B G = 5 V. Furthermore, it exhibits high linearity in both voltage and current sensitivity, with the coefficient of determination (R 2) values of 0.984 and 0.964, respectively. With their increased sensitivity and linearity, DG-ZnO-ISFETs have the potential device for next-generation biosensors. [ABSTRACT FROM AUTHOR]

A compact model of an ion-sensitive floating gate FET (ISFGFET) is presented. Unlike in the conventional ISFET, the ISFGFET has a dual gate structure, a sensing gate and a control gate. With the interplay between the control gate and the reference electrode the charging of the fluidic part of the sensor can be controlled and the sensing surface can be programmed. We present an intuitive macromodel with SPICE implementation and discuss the fluidic gating, sensitivity, chemical and electrical tuning of the ionic screening layer as well as the methods to combat the limitations such as the dielectric breakdown of the sensing oxide as well as the design trade-offs of the sensor. Additionally the model allows the integration of this new type of chemical sensor to the CMOS design flow. The proposed model relies on experimentally verified site-binding theory and double layer capacitance formulation explaining the interfacial potential. Unlike previous models we created a unified model where the sensing interface and the FET are coupled and the system is solved as such without unnecessary simplifications used earlier. The model validity is verified by comparing the results with well-established ISFET models and with experimental results. [ABSTRACT FROM AUTHOR]

The study of the effects of photoresist thickness and the use of PECVD deposited oxide hard mask layer during source/drain high dose ion implantation process in the fabrication of ion-sensitive field effect transistor (ISFET) is presented. Implementation of the new optimized process for the source/drain implant mask together with the improved process module have been successful in improving the threshold voltage (Vt) of the ISFET device from negative to more than 0.3 V. Consistent high ISFET yields of more than 90% were possible to achieve. [ABSTRACT FROM AUTHOR]

Use of an ion-sensitive field-effect transistor (ISFET) as a signal transducer in a chemical analytical system is of great scientific and application interest. Modification of the gate dielectric surface with biomolecules makes ISFET a universal platform for different applications. In this paper horseradish peroxidase (HRP, EC 1.11.1.7) was used as a label for determination of interaction between thrombin and its aptamer on the ISFET surface. The approach for thrombin detection was based on the replacement of complementary sDNA-probe containing HRP from immobilized aptamer (sDNA) with thrombin, and monitoring residual HRP activity. The biosensor was shown to detect thrombin at the level of 7·10 -7 M. [ABSTRACT FROM AUTHOR]

Wireless brain technologies are empowering basic neuroscience and clinical neurology by offering new platforms that minimize invasiveness and refine possibilities during electrophysiological recording and stimulation. Despite their advantages, most systems require on-board power supply and sizeable transmission circuitry, enforcing a lower bound for miniaturization. Designing new minimalistic architectures that can efficiently sense neurophysiological events will open the door to standalone microscale sensors and minimally invasive delivery of multiple sensors. Here we present a circuit for sensing ionic fluctuations in the brain by an ion-sensitive field effect transistor that detunes a single radiofrequency resonator in parallel. We establish sensitivity of the sensor by electromagnetic analysis and quantify response to ionic fluctuations in vitro. We validate this new architecture in vivo during hindpaw stimulation in rodents and verify correlation with local field potential recordings. This new approach can be implemented as an integrated circuit for wireless in situ recording of brain electrophysiology. • Wireless sensing of ionic fluctuations in the brain is presented. • Sensing by ion-sensitive field effect transistor tuning a radiofrequency resonator. • Sensitivity established by electromagnetic analysis and in vitro measurements. • Sensor is validated in vivo during hindpaw stimulation in rodents. • Architecture can be implemented broadly for sensing of biophysical processes. [ABSTRACT FROM AUTHOR]

• The Gouy-Chapman-Stern layer model combines the Helmholtz and the diffuse double layer of the Gouy-Chapman model to explain the development of the double-layer capacitance on the sensor's surface. • The Site-binding model is used to describe the surface charge developed at the oxide/electrolyte interface. • This paper presents a new methodology that combines these two theories, and our new method is applied to AAs (amino acids) immobilized on the sensor surface. • Moreover, our simulation work shows that each AA has a unique signature (fingerprints) that can be used to distinguish and identify each AA. In this paper, we present simulation results of a BioFET using methodology based on the Gouy-Chapman-Stern and the Site-binding models. The derived simulation approach is used to sense different amino acids, such as Arginine (R), Aspartic Acid (D) and Proline (P), functionalized with the help of a linker connected to the gate-oxide. The performance of the BioFETs is optimized while analyzing the effect of high-k dielectrics as the gate oxide. In general, the channel oxides are responsible for tuning the parameters such as sensitivity, surface potential and intrinsic buffer capacity. The variation of total surface capacitance, the second derivative of drain current and surface potential are used to uniquely identify the signatures of different amino acids. The proposed method can be helpful in defining an efficient method for label-free protein sequencing. [ABSTRACT FROM AUTHOR]

This work presents the first polymer approach to detect metal ions using AlGaN/GaN transistor-based sensor. The sensor utilised an AlGaN/GaN high electron mobility transistor-type structure by functionalising the gate area with a polyvinyl chloride (PVC) based ion selective membrane. Sensors based on this technology are portable, robust and typically highly sensitive to the target analyte; in this case Hg 2+ . This sensor showed a rapid and stable response when it was introduced to solutions of varying Hg 2+ concentrations. At pH 2.8 in a 10 −2 M KNO 3 ion buffer, a detection limit below 10 −8 M and a linear response range between 10 −8 M-10 −4 M were achieved. This detection limit is an order of magnitude lower than the reported detection limit of 10 −7 M for thioglycolic acid monolayer functionalised AlGaN/GaN HEMT devices. Detection limits of approximately 10 −7 M and 10 −6 M in 10 −2 M Cd(NO 3 ) 2 and 10 −2 M Pb(NO 3 ) 2 ion buffers were also achieved, respectively. Furthermore, we show that the apparent gate response was near-Nernstian under various conditions. X-ray photoelectron spectroscopy (XPS) experiments confirmed that the sensing membrane is reversible after being exposed to Hg 2+ solution and rinsed with deionised water. The success of this study precedes the development of this technology in selectively sensing multiple ions in water with use of the appropriate polymer based membranes on arrays of devices. [ABSTRACT FROM AUTHOR]

We present an electronic tongue system composed of an analog front-end (AFE) with embedded calibration and temperature compensation for interfacing with an array of Ion-Sensitive FETs (ISFETs) or Enzyme – Extended Gate FETs (EEGFET). The AFE consists of a floating bridge type constant voltage constant current (CVCC) structure, and transmission gates as sensor enable. It also includes a temperature readout circuit and an instrumentation amplifier for temperature compensation. The calibration algorithm is synthesized into a Field Programmable Gate Array (FPGA) and implemented onto an Application Specific Integrated Circuit (ASIC). The system shall be used to measure the pH and the concentration of calcium ions in a solution alongside a conductometric sensor system. The ISFETs used are from ITE-Poland and shall be utilized to measure pH; meanwhile, to measure the Ca 2+ concentration, EEGFETs with calcium ionophore on polyvinyl chloride (PVC) on SnO 2 /ITO/Glass thin film have been fabricated. The performance of the system using pH buffer solutions of pH 4–10, and CaCl 2 buffer concentrations of 0.001–1 M has been verified. The sensors and the AFE readout exhibited a Nernstian response (~50 mV/pH) with a very stable output having a relative standard deviation of just ~−0.4%, and a Ca 2+ sensitivity of 25.02 mV/pCa, with a drift of −6.82 mV/M-s. An on-chip version of the AFE using TSMC 0.35 µm CMOS 2P4M Technology is also presented as well as the ASIC implemented on TSMC 0.18 µm CMOS 1P6M technology. [ABSTRACT FROM AUTHOR]

In the present work, we report a novel citrate-selective sensor based on iron (III) phthalocyanine chloride-C-monoamido-Poly-n-Butyl Acrylate (Fe(III)MAPcCl-P-n-BA) modified silicon nitride and Ion sensitive field effect transistor (ISFET) structures for the electrochemical determination and estimation of the pathophysiological range of citrate. The developed capacitive sensor based on Fe(III)MAPcCl-P-n-BA had a Nernstian sensitivity of (−20.2 ± 1.3) mV/decade with a detection limit of about 7 × 10 −7 M and a linear range from 10 −6 M to 10 −1 M (RSD = 6.2%). Then, the performance of the Fe(III)MAPcCl-P-n-BA functionalized ISFET structure towards the detection of citrate has been investigated. A Nernstian sensitivity of about (−19.8 ± 1.0) mV/decade in the range from 10 −6 M to 10 −1 M was achieved (RSD = 4.8%) which covered the pathologically important clinical range of citrate. The detection limit was about 4 × 10 −7 M. The number of available recognition sites N s and the complexation constant pK were calculated using the enhanced site binding model. A side by side comparison of the developed chemical sensors based on electrolyte-insulator-Semi conductor (EIS) and ISFET structures showed similar characteristics which proves the successful miniaturization of the semiconductor based transducer. The obtained experimental data of the Fe(III)MAPcCl-P-n-BA functionalized ISFET structure were used to validate the TopSPICE ISFET/MEMFET macromodel. The obtained theoretical sensitivity was in good agreement to the experimental one which proves the successful design of the developed ISFET/MEMFET macromodel. [ABSTRACT FROM AUTHOR]

In the frame of sweat analysis, two technologies, based on either ISE or ISFET devices, were developed for the implementation of pNa potentiometric microsensors. Both of them demonstrated good sodium ion Na + detection properties with a global sensitivity of around 110 mV/pNa in NaCl-based solutions due to the use of an integrated “Ag/AgCl ink” pseudo-reference electrode. Then, in order to deal with in vivo analysis of sweat natremia, a physiological sweatband prototype was developed, consisting of pNa-ISE and pNa-ISFET electronic detection modules as well as a textile-based sweat pump. Finally, sweating process was studied during series of experiments on twenty-five healthy consenting subjects. The sodium ion concentration [Na + ] was successfully monitored in sweat during various heat exposures, demonstrating a global increase with exercise trial duration. Furthermore, a strong correlation was found between the sweat [Na + ] concentration and the subject's internal temperature θ , allowing monitoring the subject's heat stress state. All in all, the relevance of the Na + ion analysis was demonstrated for the physiological stress monitoring and pNa potentiometric microsensors were shown to be very promising for the development of smart sweatbands. [ABSTRACT FROM AUTHOR]

The work presents implementing a low cost pH sensing system for biological applications in a flexible electronics process. As a part of the system the work describes an ion sensitive field effect transistor, using indium tin oxide (ITO) as a sensing layer and gold as a reference electrode, on a flexible substrate. The devices presented here are designed and fabricated using the thin film transistor (TFT) display technology at the Arizona State University Flexible Electronics and Display Center. It was observed that ITO has a sensitivity of 50 mV/pH. The work also discusses the variability in these devices and signal processing that could be used to calibrate them. Toward this end, a readout circuit designed in a 0.5 μm CMOS process is presented to interface with the sensors. [ABSTRACT FROM AUTHOR]

A GaN-based ion sensitive field-effect transistor (ISFET) prepared by a hydrogen peroxide (H 2 O 2 ) treatment is fabricated and studied. A 3-nm-thick Ga x O y layer formed by an immersion in H 2 O 2 solution is examined and confirmed by EDS and XPS analyses. Experimentally, the studied pH-ISFET presents a higher voltage sensitivity (54.88 mV/pH), a higher current sensitivity (−56.09 μA/pH mm), a lower drift rate (1.41 μA/h mm), an extremely low hysteresis (0.4 mV), and a lower voltage decay rate (−0.14 mV/pH day) after 28 days. Moreover, insignificant interference effects from Na + and K + ions were observed. Thus, the studied GaN-based ISFET utilizing an H 2 O 2 treatment promises to fabricate high-performance pH sensing applications. [ABSTRACT FROM AUTHOR]

We present a highly sensitive chemical sensor system including a chip with an array of silicon nanowire ISFETs and a CMOS chip with custom-designed signal-conditioning circuitry. The CMOS circuitry, comprising 8 sigma–delta (Σ–Δ) modulators and 8 current-to-frequency converters, has been interfaced to each of the nanowires to apply a constant voltage for measuring the respective current through the nanowire. Each nanowire has a dedicated readout channel, so that no multiplexing is required, which helps to avoid leakage current issues. The analog signal has been digitized on chip and transmitted to a host PC via a FPGA. The system has been successfully fabricated and tested and features, depending on the settings, noise values as low as 8.2 pA RMS and a resolution of 13.3 bits while covering an input current range from 200 pA to 3 μA. The two readout architectures (Σ–Δ and current to frequency) have been compared, and measurements showing the advantages of combining a CMOS readout with silicon nanowire sensors are presented: (1) simultaneous readout of different silicon nanowires for high-temporal-resolution experiments and parallel sensor experiments (results from pH and KCl concentration sweeps are presented); (2) high speed measurements showing how the CMOS chip can enhance the performance of the nanowire sensors by compensating its non-idealities as a consequence of hysteresis. [ABSTRACT FROM AUTHOR]

• Use of electrolytically gated SOI pFinFETs as bioFETs. • Detection of DNA with nanoscale bioFETs. • Evaluation of low-frequency noise in bioFETs between 1 Hz and 100 Hz. • Determination of optimum signal-to-noise ratio. We experimentally demonstrate the use of electrolytically gated SOI pFinFETs employed as bioFETs for the detection of single-stranded DNA and evaluate their low-frequency noise in the range between 1 Hz and 100 Hz. Both channel length and overdrive voltage dependencies are analyzed, showing the best (i.e., highest) signal to noise ratio for the devices with their gates biased around the threshold voltage, with little to no dependence on the channel length. [ABSTRACT FROM AUTHOR]

Highlights: [•] A high performance high density vertically stacked SiNW FET structure has been electrically characterized for biosensor applications. [•] Structure has high drive currents 1.3mA/μm (normalized to an average NW diameter of 30nm at V SG =3V, and V d =50mV). [•] Excellent I on/I off ratios >106. [•] Steep subthreshold slopes down to SS<75mV/dec. [•] High transconductances g m >10μS. [Copyright &y& Elsevier]

Abstract: A dual-gate (DG) ion sensitive field effect transistor (ISFET) using capacitance coupling effect has recently been proposed to overcome the Nernst limitation as 59mV/pH. In this study, we focus on the analysis of sensing characteristics by various oxide capacitances and channel thickness using intensive measurement on conventional fully depleted (FD) silicon-on-insulator (SOI) based DG ISFET. The enlarged oxide capacitance and reductive channel thickness enhance the capacitive coupling effect and increase sensitivity of DG ISFET. And also, the thin channel thickness reduced the leakage current in the DG operation. These will be very promising techniques for high performance biosensor application. [Copyright &y& Elsevier]

Abstract: Cell-based screening assays are now widely used for identifying compounds that serve as ion channel modulators. However, instrumentation for the automated, real-time analysis of ion flux from clonal and primary cells is lacking. This study describes the initial development of an ion-sensitive field effect transistor (ISFET)-based screening assay for the acquisition of K+ efflux data from cells cultured in multi-well plates. Silicon-based K+-sensitive ISFETs were tested for their electrical response to varying concentrations of KCl and were found to display a linear response relationship to KCl in the range of 10µM–1mM. The ISFETs, along with reference electrodes, were inserted into fast-flow chambers containing either human colonic T84 epithelial cells or U251-MG glioma cells. Application of the Ca2+ ionophore A23187 (1µM), to activate Ca2+-activated non-selective cation (NSC) channels (T84 cells) and large conductance Ca2+-activated K+ (BK) channels (U251 cells), resulted in time-dependent increases in the extracellular K+ concentration ([K+]o) as measured with the ISFETs. Treatment of the cells with blockers of either the NSC or BK channels, caused a strong inhibition of the A23187-induced increase in [K+]o. These results were consistent with ion current measurements obtained using the whole-cell arrangement of the patch clamp procedure. In addition, K+ efflux data could be acquired in parallel from multiple cell chambers using the ISFET sensors. Given the non-invasive properties of the probes, the ISFET-based assay should be adaptable for screening ion channels in various cell types. [Copyright &y& Elsevier]

Performance of autonomous pH sensors is evaluated by comparing in situ data to independent bench-top measurements of pH and to co-located pH, O 2 , and p CO 2 sensors. While the best practice is always to deploy a properly calibrated sensor, the lengthy time period required for sensor conditioning and calibration often results in sensor deployment without comprehensive calibration. Quality control (QC) procedures are examined to determine the errors associated with different in situ calibration approaches and lay a framework for best practices. Sensor packages employing the Honeywell Durafet remained stable across multiple deployments for over nine months. However, sensor performance was often limited by biofouling. Regional empirical relationships for estimating carbonate system parameters are shown to enable identification of otherwise indistinguishable sensor offset and drift when multiple sensor types are co-located. Uncertainty is determined by calibration approach and must be quantified on a case-by-case basis. Our results indicate that the Durafet is capable of accuracy, relative to a chosen reference, of better than 0.03 pH units over multiple months. Accuracy is improved when a robust shore-side calibration is performed, an independent means of QC is available throughout a deployment, and effective biofouling prevention measures are taken. [ABSTRACT FROM AUTHOR]

Abstract: We present a wireless sensor network to measure pH, dissolved oxygen (DO), and temperature for use in algae cultivation. The pH is measured using ion sensitive field effect transistor (ISFET) technology, which is more robust and has a faster response than traditional glass pH electrodes. A custom circuit drives the ISFET sensor and interfaces with an ANT wireless network system. The wireless network consists of a network hub which can service up to 8 sensor nodes and a series of relays to transmit the data to a PC. The data is logged with a custom LabVIEW program. In this work, we demonstrate operation of this network using 5 sensors (3 ISFET pH, 1 DO, 1 temp), one hub, and two relay units. The network was used to collect data for 42days from a 1600L raceway tank growing Scenedesmus dimorphus. In that time, the network did not experience any failures beyond what can be mitigated with additional battery capacity and improved construction methods. At the end of the growth cycle, the daily variation in dissolved oxygen was observed to closely track the optical density measurements. [Copyright &y& Elsevier]

Highlights: [•] A high density vertically stacked SiNW and FinFET with ultra-thin (15–30nm) and long structures has been fabricated successfully. [•] 3D devices features highly robust stacked structures for biosensor applications. [•] Fully top-down CMOS compatible process introduced. [•] Sensor can be integrated heterogeneously. [ABSTRACT FROM AUTHOR]

Highlights: [•] Long channel (L >500nm) junctionless NW/fin transistors were investigated through 3D TCAD simulations. [•] Mildly doped N d =1×1019 cm−3 structures with F w <20nm and ε r =1.7 have promising characteristics for sensors. [•] These structures have V th ~0V and high relative sensitivities in the subthreshold regime SS>95%. [•] They also have high transconductance values at threshold g m,Vfg=0V >10nS, and low subthreshold slopes SS~60mV/dec. [•] Finally they were found to have high saturation currents I d,max ~1–10μA and high I on/I off >104–1010 ratios. [Copyright &y& Elsevier]

Abstract: AlGaN/GaN heterostructure-based devices can be engineered through heterostructure design to have a high transconductance near zero gate–drain voltage, potentially enabling high sensitivity, reference electrode free, ion sensing. As a proof of concept, these devices were coated with a PVC-based membrane containing a plasticizer and an ionophore to detect nitrate ions in solution. The sensor response is measured as a change in conductivity across two contacts using a Kelvin probe (or four-contact) geometry, with the current between the two outer contacts kept constant. We show that this sensor for nitrate is sensitive and stable with a rapid response time (i.e. less than 60s). The detection limit remains consistently low over multiple runs/days. In a 0.1M KH2PO4 ion buffer, a detection limit of less than 1×10−6 M and a linear response range of 10−6–10−3 M were achieved. Furthermore, detection limits of approximately 10−6 M and 10−4 M in 0.1M K2SO4 and 0.1M KCl ion buffers, respectively, were demonstrated. In a 0.1M KH2PO4 ion buffer, there was minimal change in sensor response upon addition of KOH increasing the pH from approximately 4–11. As a control, devices without a PVC membrane coating were tested under identical conditions and exhibited negligible response to nitrate ion exposure. Furthermore, using transistor theory, we show that the apparent gate response is near-Nenrstian under a variety of conditions. The success of this study paves the way for extending this technology to selectively sensing multiple ions in water through incorporation of the appropriate polymer based membranes on arrays of devices. [Copyright &y& Elsevier]

Abstract: In recent years, there has been an increasing interest in the monitoring and controlling of pH. It has become an important aspect of many industrial wastewater and water quality treatment processes. At the same time, the demand for smaller electronic devices used for various industrial, commercial, and research applications has greatly increased. In this paper, we propose a fabrication method of ion-sensitive field effect transistor (ISFET) using micro–electro-mechanical systems (MEMS) techniques for pH sensing application. The novelty of this device lies in the detection of target solution with volumes in the sub-microliter range. With proper electrical packaging, our ISFET chip has been able to detect the pH values of 2.5μL solutions. The results reveal a linearity of pH measurement with a corresponding sensitivity of 10.7mV/pH. Furthermore, Nernst equation is employed to analyze the performance, and a promising scheme to improve the sensitivity while measuring tiny solutions is proposed. This achievement has the potential to satisfy the research demands in various areas including chemistry, biology and medicine. [Copyright &y& Elsevier]

Abstract: The electrical detection of DNA methylation based biomarkers using semiconductor technology shows great promise for early cancer screening. Presented is the very first proof-of-concept example of using CMOS-based technology for real-time DNA methylation detection using Ion-Sensitive Field-Effect Transistors (ISFETs). An electrochemical label-free approach was applied in two gene assays, each one of which incorporated the sequences of DAPK1 and CDKN2A/p16-INK4 (p16) gene promoters at a both methylated and unmethylated state, performing isothermal methylation-specific amplification and detection both in-tube and on-chip (real-time). Good discrimination was shown between the two states, achieving a very good average pH signal change for the methylated state of 1.91 for DAPK1 assay and of 1.58 for p16 assay in the tube test. The real-time on-chip test showed similarly good real-time differential signal change in favour of methylated DNA, reaching 37mV for DAPK1 assay and 23mV for p16 assay, validating the results from the proof-of-concept test of pH-LAMP in-tube while confirming the sensitivity of real-time methylation-specific pH-LAMP on-chip. [Copyright &y& Elsevier]

Abstract: The CIP stability of pH sensitive ion-sensitive field-effect transistors based on AlGaN/GaN heterostructures was investigated. For epitaxial AlGaN/GaN films with high structural quality, CIP tests did not degrade the sensor surface and pH sensitivities of 55–58mV/pH were achieved. Several different passivation schemes based on SiO x , SiN x , AlN, and nanocrystalline diamond were compared with special attention given to compatibility to standard microelectronic device technologies as well as biocompatibility of the passivation films. The CIP stability was evaluated with a main focus on the morphological stability. All stacks containing a SiO2 or an AlN layer were etched by the NaOH solution in the CIP process. Reliable passivations withstanding the NaOH solution were provided by stacks of ICP-CVD grown and sputtered SiN x as well as diamond reinforced passivations. Drift levels about 0.001pH/h and stable sensitivity over several CIP cycles were achieved for optimized sensor structures. [Copyright &y& Elsevier]

Abstract: This work describes the development and testing of a microfabricated sensor for rapid cell growth monitoring, especially focused on yeast quality assessment for wine applications. The device consists of a NMOS ISFET sensor with Si3N4 gate, able to indirectly monitor extracellular metabolism through pH variation of the medium, and a solid-state reference electrode implemented with PVC membranes doped with lipophilic salts (tetrabutylammonium-tetrabutylborate (TBA-TBB) and Potassium tetrakis(4-chlorphenyl)borate (KTClpB)). The use of a solid state reference electrode enables the implementation of a large number of cell assays in parallel, without the need of external conventional reference electrodes. Microbial growth testing has been performed both in standard culture conditions and on chip at different concentrations of ethanol in order to carry out a commonly used screening of wine yeast strains. Cell growth tests can be performed in few hours, providing a fast, sensitive and low cost analysis with respect to the conventional procedures. [Copyright &y& Elsevier]

Abstract: A role of the dielectric silica nanoparticle (SiO2 NP) in nanomaterial chemoresistors and ion-sensitive field-effect transistors (ISFET) is demonstrated in this study. Single-walled carbon nanotubes (SWCNT) and indium oxide nanoparticles (In2O3 NP) are layer-by-layer self-assembled alternately with oppositely charged polyelectrolytes, respectively. Nanomaterial multilayer thin-film is patterned using photolithography and electrochemically characterized in various pH buffers. The pH sensors are implemented as resistor and transistor in absence and presence of SiO2 NP layer. We observed tunable sensitivity and linearity of output current flowing through the conducting channel in SWCNT chemoresistor and ISFET. The role of SiO2 NP is proven to modulate and linearize the sensitivity to pH. The linearization is attributed to a positive shift in pH gating voltage in p-type semiconducting SWCNTs. On the other hand, a tunable sensitivity is observed whereas the linearization is not demonstrated in In2O3 NP ISFETs. The increased sensitivity with SiO2 NP in acidic region is caused by a positive shift in gate voltage due to the protonation of the surface hydroxyl groups. This facile modulation and linearization of the electrochemical sensitivity in semiconducting nanomaterial thin-film device by means of the additional SiO2 NP layer is useful for developing various functional nanomaterial-based biosensors. [Copyright &y& Elsevier]

Abstract: High density (7–10NW/μm) SiNW arrays of up to 16 nanowires vertically stacked with diameter widths below 20nm have been successfully fabricated to create highly sensitive 3D FETs for biosensing applications. In order to take advantage of the increased sensing surface area that nanoscale 3D devices offer and improve the mechanical characteristics of the suspended sensing channels, fin-type structures (height/width ratio >1) are also being investigated. The vertical stacking allows higher utilization of the bulk Si. Higher output currents are expected as the number of conduction channels increases. 3D TCAD simulations have been done for up to three channels to investigate different device characteristics to achieve high sensitivities. Both NWs and Fins have been found to offer very high sensitivities through simulations especially for short (2μm) channels, low channel doping concentrations (boron: 1015 cm−3), and thin structures (width <30nm) when applying an external sensing gate potential variation of ΔΨ =90mV. [Copyright &y& Elsevier]

Abstract: We describe a complete lab-on-a-chip type ion-sensitive chemical sensor array system for imaging proton concentration and flow. The core of the imaging system relies on a 715.8μm×715.8μm large 64×64-pixel ISFET sensor array that is designed and fabricated in a conventional 4-metal 0.35μm CMOS process along with readout circuitry and additional electronics. The high-speed and real-time data acquisition of ∼100frame per second (fps), 40μs per pixel, results in a large amount of data that is streamed to the hard disk. Image reconstruction methods allow visualization of the dynamic behavior of chemical substances and ionic spreads over the sensor array at a resolution of the size of a pixel. The functionalities of the on-chip ion-camera device are demonstrated using appropriate acid and alkaline solutions. A pH sensitivity of 20mV/pH was achieved without modification to the foundry processed chip. [Copyright &y& Elsevier]

Abstract: Low sensitivity and poor reliability currently limit the applications of solid-state bio-chemical sensors. We demonstrate an electrolyte-insulator-semiconductor (EIS) sensor with a large capacitance, near-Nernst-limit pH sensitivity, and good reliability by integrating an ensemble of Si nanowires (NWs) for the first time. The NWs were fabricated by using the electroless wet etching technique. An Al2O3/SiO2 bilayer coating was employed as a sensing membrane. The EIS sensors with 3.8μm long NWs exhibited about 8 times larger capacitance than that of a planar type EIS sensors that were fabricated using the same fabrication scheme without integrating NWs. The measured pH sensitivity at room temperature was 60.2mV/pH, which is higher than the theoretical Nernstian of 59mV/pH. Our results and analysis clearly indicate that ultra-sensitive pH sensing can be realized with optimized NW integrated EIS sensors. [Copyright &y& Elsevier]