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Field-Effect Sensors: From pH Sensing to Biosensing

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A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 38005

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Prof. Dr. Michael J. Schöning

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Director, Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Heinrich-Mußmann-Str. 1, 52428 Jülich, Germany
Interests: silicon-based chemical sensors; label-free biosensing; field-effect devices; micro- and nanosystem technology; sensor applications
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Sven Ingebrandt

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Director, Institute of Materials in Electrical Engineering 1, RWTH Aachen University, Sommerfeldstr. 24, 52074 Aachen, Germany
Interests: biosensors; bioelectronics; field-effect transistors; nanowires; 2D materials; wearables; neuroimplants; micro- and nanosystems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The groundbreaking Short Communication by Piet Bergveld in 1970 (“Development of an ion-sensitive solid-date device for neurophysiological measurements”, IEEE Trans. on Biomed. Eng.) has stimulated and attracted a multitude of (young) scientists within the last five decades working with ion-sensitive field-effect devices for chemical sensing and biosensing, distinctly enhancing the device structures, materials, (bio)receptor layers, electronic amplifier circuits, system integration, and sensor performance as well as broadening the areas of applications. Mainly, three types of (bio-)chemical field-effect sensors are discussed in literature, i.e., ISFETs (ion-sensitive field-effect transistors), most of the time called nanowire devices in nanometer dimensions, LAPS (light-addressable potentiometric sensors), and capacitive EIS (electrolyte–insulator–semiconductor) sensors. This Special Issue is devoted to the different types of field-effect devices and to the scopes of their applications, compiling examples of state-of-the-art technologies. The topic may include but is not exclusively related to:

Device concepts for field-effect sensors for (bio-)chemical sensing;
Modelling and theory of field-effect sensors;
Nanomaterial-modified field-effect (bio-)chemical sensors;
Field-effect sensors for biomedical analysis, food control, and environmental monitoring;
Field-effect sensors for recording of neuronal and cell-based signals;
Chemical imaging with field-effect sensors

Prof. Dr. Michael J. Schöning
Prof. Dr. Sven Ingebrandt
Guest Editors

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Published Papers (12 papers)

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Research

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15 pages, 2803 KiB

Open AccessArticle

Planar Junctionless Field-Effect Transistor for Detecting Biomolecular Interactions

by Rajendra P. Shukla, J. G. Bomer, Daniel Wijnperle, Naveen Kumar, Vihar P. Georgiev, Aruna Chandra Singh, Sivashankar Krishnamoorthy, César Pascual García, Sergii Pud and Wouter Olthuis

Sensors 2022, 22(15), 5783; https://doi.org/10.3390/s22155783 - 2 Aug 2022

Cited by 8 | Viewed by 3741

Abstract

Label-free field-effect transistor-based immunosensors are promising candidates for proteomics and peptidomics-based diagnostics and therapeutics due to their high multiplexing capability, fast response time, and ability to increase the sensor sensitivity due to the short length of peptides. In this work, planar junctionless field-effect transistor sensors (FETs) were fabricated and characterized for pH sensing. The device with SiO₂ gate oxide has shown voltage sensitivity of 41.8 ± 1.4, 39.9 ± 1.4, 39.0 ± 1.1, and 37.6 ± 1.0 mV/pH for constant drain currents of 5, 10, 20, and 50 nA, respectively, with a drain to source voltage of 0.05 V. The drift analysis shows a stability over time of −18 nA/h (pH 7.75), −3.5 nA/h (pH 6.84), −0.5 nA/h (pH 4.91), 0.5 nA/h (pH 3.43), corresponding to a pH drift of −0.45, −0.09, −0.01, and 0.01 per h. Theoretical modeling and simulation resulted in a mean value of the surface states of 3.8 × 10¹⁵/cm² with a standard deviation of 3.6 × 10¹⁵/cm². We have experimentally verified the number of surface sites due to APTES, peptide, and protein immobilization, which is in line with the theoretical calculations for FETs to be used for detecting peptide-protein interactions for future applications. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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18 pages, 5014 KiB

Open AccessArticle

Rational Design of Field-Effect Sensors Using Partial Differential Equations, Bayesian Inversion, and Artificial Neural Networks

by Amirreza Khodadadian, Maryam Parvizi, Mohammad Teshnehlab and Clemens Heitzinger

Sensors 2022, 22(13), 4785; https://doi.org/10.3390/s22134785 - 24 Jun 2022

Cited by 12 | Viewed by 2538

Abstract

Silicon nanowire field-effect transistors are promising devices used to detect minute amounts of different biological species. We introduce the theoretical and computational aspects of forward and backward modeling of biosensitive sensors. Firstly, we introduce a forward system of partial differential equations to model the electrical behavior, and secondly, a backward Bayesian Markov-chain Monte-Carlo method is used to identify the unknown parameters such as the concentration of target molecules. Furthermore, we introduce a machine learning algorithm according to multilayer feed-forward neural networks. The trained model makes it possible to predict the sensor behavior based on the given parameters. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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8 pages, 1393 KiB

Open AccessCommunication

Efficient Illumination for a Light-Addressable Potentiometric Sensor

by Tatsuo Yoshinobu and Ko-ichiro Miyamoto

Sensors 2022, 22(12), 4541; https://doi.org/10.3390/s22124541 - 16 Jun 2022

Viewed by 1754

Abstract

A light-addressable potentiometric sensor (LAPS) is a chemical sensor that is based on the field effect in an electrolyte–insulator–semiconductor structure. It requires modulated illumination for generating an AC photocurrent signal that responds to the activity of target ions on the sensor surface. Although high-power illumination generates a large signal, which is advantageous in terms of the signal-to-noise ratio, excess light power can also be harmful to the sample and the measurement. In this study, we tested different waveforms of modulated illuminations to find an efficient illumination for a LAPS that can enlarge the signal as much as possible for the same input light power. The results showed that a square wave with a low duty ratio was more efficient than a sine wave by a factor of about two. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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14 pages, 4620 KiB

Open AccessArticle

Realization of a PEDOT:PSS/Graphene Oxide On-Chip Pseudo-Reference Electrode for Integrated ISFETs

by Marcel Tintelott, Tom Kremers, Sven Ingebrandt, Vivek Pachauri and Xuan Thang Vu

Sensors 2022, 22(8), 2999; https://doi.org/10.3390/s22082999 - 14 Apr 2022

Cited by 9 | Viewed by 3275

Abstract

A stable reference electrode (RE) plays a crucial role in the performance of an ion-sensitive field-effect transistor (ISFET) for bio/chemical sensing applications. There is a strong demand for the miniaturization of the RE for integrated sensor systems such as lab-on-a-chip (LoC) or point-of-care (PoC) applications. Out of several approaches presented so far to integrate an on-chip electrode, there exist critical limitations such as the effect of analyte composition on the electrode potential and drifts during the measurements. In this paper, we present a micro-scale solid-state pseudo-reference electrode (pRE) based on poly(3,4-ethylene dioxythiophene): poly(styrene sulfonic acid) (PEDOT:PSS) coated with graphene oxide (GO) to deploy with an ion-sensitive field-effect transistor (ISFET)-based sensor platform. The PEDOT:PSS was electropolymerized from its monomer on a micro size gold (Au) electrode and, subsequently, a thin GO layer was deposited on top. The stability of the electrical potential and the cross-sensitivity to the ionic strength of the electrolyte were investigated. The presented pRE exhibits a highly stable open circuit potential (OCP) for up to 10 h with a minimal drift of ~0.65 mV/h and low cross-sensitivity to the ionic strength of the electrolyte. pH measurements were performed using silicon nanowire field-effect transistors (SiNW-FETs), using the developed pRE to ensure good gating performance of electrolyte-gated FETs. The impact of ionic strength was investigated by measuring the transfer characteristic of a SiNW-FET in two electrolytes with different ionic strengths (1 mM and 100 mM) but the same pH. The performance of the PEDOT:PSS/GO electrode is similar to a commercial electrochemical Ag/AgCl reference electrode. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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10 pages, 4057 KiB

Open AccessCommunication

Simultaneous In Situ Imaging of pH and Surface Roughening during the Progress of Crevice Corrosion of Stainless Steel

by Ko-ichiro Miyamoto, Rinya Hiramitsu, Carl Frederik Werner and Tatsuo Yoshinobu

Sensors 2022, 22(6), 2246; https://doi.org/10.3390/s22062246 - 14 Mar 2022

Cited by 8 | Viewed by 2219

Abstract

Stainless steel plays an important role in industry due to its anti-corrosion characteristic. It is known, however, that local corrosion can damage stainless steel under certain conditions. In this study, we developed a novel measurement system to observe crevice corrosion, which is a local corrosion that occurs inside a narrow gap. In addition to pH imaging inside the crevice, another imaging technique using an infrared light was combined to simultaneously visualize surface roughening of the test piece. According to experimental results, the lowering of local pH propagated inside the crevice, and after that, the surface roughening started and expanded due to propagation of corrosion. The real-time measurement of the pH distribution and the surface roughness can be a powerful tool to investigate the crevice corrosion. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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12 pages, 2512 KiB

Open AccessArticle

High Spatial Resolution Ion Imaging by Focused Electron-Beam Excitation with Nanometric Thin Sensor Substrate

by Kiyohisa Nii, Wataru Inami and Yoshimasa Kawata

Sensors 2022, 22(3), 1112; https://doi.org/10.3390/s22031112 - 1 Feb 2022

Cited by 2 | Viewed by 2278

Abstract

We developed a high spatially-resolved ion-imaging system using focused electron beam excitation. In this system, we designed a nanometric thin sensor substrate to improve spatial resolution. The principle of pH measurement is similar to that of a light-addressable potentiometric sensor (LAPS), however, here the focused electron beam is used as an excitation carrier instead of light. A Nernstian-like pH response with a pH sensitivity of 53.83 mV/pH and linearity of 96.15% was obtained. The spatial resolution of the imaging system was evaluated by applying a photoresist to the sensing surface of the ion-sensor substrate. A spatial resolution of 216 nm was obtained. We achieved a substantially higher spatial resolution than that reported in the LAPS systems. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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17 pages, 3241 KiB

Open AccessArticle

An Array of On-Chip Integrated, Individually Addressable Capacitive Field-Effect Sensors with Control Gate: Design and Modelling

by Arshak Poghossian, Rene Welden, Vahe V. Buniatyan and Michael J. Schöning

Sensors 2021, 21(18), 6161; https://doi.org/10.3390/s21186161 - 14 Sep 2021

Cited by 6 | Viewed by 1985

Abstract

The on-chip integration of multiple biochemical sensors based on field-effect electrolyte-insulator-semiconductor capacitors (EISCAP) is challenging due to technological difficulties in realization of electrically isolated EISCAPs on the same Si chip. In this work, we present a new simple design for an array of on-chip integrated, individually electrically addressable EISCAPs with an additional control gate (CG-EISCAP). The existence of the CG enables an addressable activation or deactivation of on-chip integrated individual CG-EISCAPs by simple electrical switching the CG of each sensor in various setups, and makes the new design capable for multianalyte detection without cross-talk effects between the sensors in the array. The new designed CG-EISCAP chip was modelled in so-called floating/short-circuited and floating/capacitively-coupled setups, and the corresponding electrical equivalent circuits were developed. In addition, the capacitance-voltage curves of the CG-EISCAP chip in different setups were simulated and compared with that of a single EISCAP sensor. Moreover, the sensitivity of the CG-EISCAP chip to surface potential changes induced by biochemical reactions was simulated and an impact of different parameters, such as gate voltage, insulator thickness and doping concentration in Si, on the sensitivity has been discussed. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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14 pages, 15982 KiB

Open AccessArticle

Comprehensive Analytical Modelling of an Absolute pH Sensor

by Cristina Medina-Bailon, Naveen Kumar, Rakshita Pritam Singh Dhar, Ilina Todorova, Damien Lenoble, Vihar P. Georgiev and César Pascual García

Sensors 2021, 21(15), 5190; https://doi.org/10.3390/s21155190 - 30 Jul 2021

Cited by 11 | Viewed by 3572

Abstract

In this work, we present a comprehensive analytical model and results for an absolute pH sensor. Our work aims to address critical scientific issues such as: (1) the impact of the oxide degradation (sensing interface deterioration) on the sensor’s performance and (2) how to achieve a measurement of the absolute ion activity. The methods described here are based on analytical equations which we have derived and implemented in MATLAB code to execute the numerical experiments. The main results of our work show that the depletion width of the sensors is strongly influenced by the pH and the variations of the same depletion width as a function of the pH is significantly smaller for hafnium dioxide in comparison to silicon dioxide. We propose a method to determine the absolute pH using a dual capacitance system, which can be mapped to unequivocally determine the acidity. We compare the impact of degradation in two materials: SiO

_{2}

and HfO

_{2}

, and we illustrate the acidity determination with the functioning of a dual device with SiO

_{2}

. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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Review

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15 pages, 2026 KiB

Open AccessReview

Field-Effect Sensors Using Biomaterials for Chemical Sensing

by Chunsheng Wu, Ping Zhu, Yage Liu, Liping Du and Ping Wang

Sensors 2021, 21(23), 7874; https://doi.org/10.3390/s21237874 - 26 Nov 2021

Cited by 6 | Viewed by 3240

Abstract

After millions of years of evolution, biological chemical sensing systems (i.e., olfactory and taste systems) have become very powerful natural systems which show extreme high performances in detecting and discriminating various chemical substances. Creating field-effect sensors using biomaterials that are able to detect specific target chemical substances with high sensitivity would have broad applications in many areas, ranging from biomedicine and environments to the food industry, but this has proved extremely challenging. Over decades of intense research, field-effect sensors using biomaterials for chemical sensing have achieved significant progress and have shown promising prospects and potential applications. This review will summarize the most recent advances in the development of field-effect sensors using biomaterials for chemical sensing with an emphasis on those using functional biomaterials as sensing elements such as olfactory and taste cells and receptors. Firstly, unique principles and approaches for the development of these field-effect sensors using biomaterials will be introduced. Then, the major types of field-effect sensors using biomaterials will be presented, which includes field-effect transistor (FET), light-addressable potentiometric sensor (LAPS), and capacitive electrolyte–insulator–semiconductor (EIS) sensors. Finally, the current limitations, main challenges and future trends of field-effect sensors using biomaterials for chemical sensing will be proposed and discussed. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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15 pages, 3177 KiB

Open AccessReview

Chemically Induced pH Perturbations for Analyzing Biological Barriers Using Ion-Sensitive Field-Effect Transistors

by Tatsuro Goda

Sensors 2021, 21(21), 7277; https://doi.org/10.3390/s21217277 - 1 Nov 2021

Cited by 1 | Viewed by 2416

Abstract

Potentiometric pH measurements have long been used for the bioanalysis of biofluids, tissues, and cells. A glass pH electrode and ion-sensitive field-effect transistor (ISFET) can measure the time course of pH changes in a microenvironment as a result of physiological and biological activities. However, the signal interpretation of passive pH sensing is difficult because many biological activities influence the spatiotemporal distribution of pH in the microenvironment. Moreover, time course measurement suffers from stability because of gradual drifts in signaling. To address these issues, an active method of pH sensing was developed for the analysis of the cell barrier in vitro. The microenvironmental pH is temporarily perturbed by introducing a low concentration of weak acid (NH₄⁺) or base (CH₃COO⁻) to cells cultured on the gate insulator of ISFET using a superfusion system. Considering the pH perturbation originates from the semi-permeability of lipid bilayer plasma membranes, induced proton dynamics are used for analyzing the biomembrane barriers against ions and hydrated species following interaction with exogenous reagents. The unique feature of the method is the sensitivity to the formation of transmembrane pores as small as a proton (H⁺), enabling the analysis of cell–nanomaterial interactions at the molecular level. The new modality of cell analysis using ISFET is expected to be applied to nanomedicine, drug screening, and tissue engineering. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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23 pages, 5263 KiB

Open AccessReview

Process Variability in Top-Down Fabrication of Silicon Nanowire-Based Biosensor Arrays

by Marcel Tintelott, Vivek Pachauri, Sven Ingebrandt and Xuan Thang Vu

Sensors 2021, 21(15), 5153; https://doi.org/10.3390/s21155153 - 29 Jul 2021

Cited by 24 | Viewed by 5259

Abstract

Silicon nanowire field-effect transistors (SiNW-FET) have been studied as ultra-high sensitive sensors for the detection of biomolecules, metal ions, gas molecules and as an interface for biological systems due to their remarkable electronic properties. “Bottom-up” or “top-down” approaches that are used for the fabrication of SiNW-FET sensors have their respective limitations in terms of technology development. The “bottom-up” approach allows the synthesis of silicon nanowires (SiNW) in the range from a few nm to hundreds of nm in diameter. However, it is technologically challenging to realize reproducible bottom-up devices on a large scale for clinical biosensing applications. The top-down approach involves state-of-the-art lithography and nanofabrication techniques to cast SiNW down to a few 10s of nanometers in diameter out of high-quality Silicon-on-Insulator (SOI) wafers in a controlled environment, enabling the large-scale fabrication of sensors for a myriad of applications. The possibility of their wafer-scale integration in standard semiconductor processes makes SiNW-FETs one of the most promising candidates for the next generation of biosensor platforms for applications in healthcare and medicine. Although advanced fabrication techniques are employed for fabricating SiNW, the sensor-to-sensor variation in the fabrication processes is one of the limiting factors for a large-scale production towards commercial applications. To provide a detailed overview of the technical aspects responsible for this sensor-to-sensor variation, we critically review and discuss the fundamental aspects that could lead to such a sensor-to-sensor variation, focusing on fabrication parameters and processes described in the state-of-the-art literature. Furthermore, we discuss the impact of functionalization aspects, surface modification, and system integration of the SiNW-FET biosensors on post-fabrication-induced sensor-to-sensor variations for biosensing experiments. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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Other

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7 pages, 716 KiB

Open AccessPerspective

Technical Perspectives on Applications of Biologically Coupled Gate Field-Effect Transistors

by Toshiya Sakata

Sensors 2022, 22(13), 4991; https://doi.org/10.3390/s22134991 - 1 Jul 2022

Cited by 2 | Viewed by 3038

Abstract

Biosensing technologies are required for point-of-care testing (POCT). We determine some physical parameters such as molecular charge and mass, redox potential, and reflective index for measuring biological phenomena. Among such technologies, biologically coupled gate field-effect transistor (Bio-FET) sensors are a promising candidate as a type of potentiometric biosensor for the POCT because they enable the direct detection of ionic and biomolecular charges in a miniaturized device. However, we need to reconsider some technical issues of Bio-FET sensors to expand their possible use for biosensing in the future. In this perspective, the technical issues of Bio-FET sensors are pointed out, focusing on the shielding effect, pH signals, and unique parameters of FETs for biosensing. Moreover, other attractive features of Bio-FET sensors are described in this perspective, such as the integration and the semiconductive materials used for the Bio-FET sensors. Full article

(This article belongs to the Special Issue Field-Effect Sensors: From pH Sensing to Biosensing)

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