Label-free Biosensing Applications Research Articles

A CMOS-integrated terahertz near-field sensor based on an ultra-strongly coupled meta-atom

Recently, plasmonic-based sensors operating in the terahertz frequency range have emerged as perspective tools for rapid and efficient label-free biosensing applications. In this work, we present a fully electronic approach allowing us to achieve state-of-the-art sensitivity by utilizing a near-field-coupled electronic sensor. We demonstrate that the proposed concept enables the efficient implementation and probing of a so-called ultra-strongly coupled sub-wavelength meta-atom as well as a single resonant circuit, allowing to limit the volume of material under test down to a few picoliter range. The sensor has been monolithically integrated into a cost-efficient silicon-based CMOS technology. Our findings are supported by both numerical and analytical models and validated through experiments. They lay the groundwork for near-future developments, outlining the perspectives for a terahertz microfluidic lab-on-chip dielectric spectroscopy sensor.

Dielectrically-Modulated GANFET Biosensor for Label-Free Detection of DNA and Avian Influenza Virus: Proposal and Modeling

This paper introduces a novel device called the Gate All Around Engineered Gallium Nitride Field Effect Transistor (GAAE-GANFET), designed specifically for label-free biosensing applications. This innovative gate-all-around engineering in GANFET integrates various device engineering techniques, such as channel engineering, gate engineering, and oxide engineering, to enhance biosensing performance. The channel engineering techniques refer to the use of a gallium nitride channel with a step-graded doping profile, divided into three distinct regions. In contrast, the gate engineering technique refers to the cylindrical split-gate-underlap architecture. The oxide engineering technique involves stacking Al2O3 and HfO2. Moreover, this biosensor incorporates two-sided gate underlap cavities that facilitate the immobilization of biomolecules. These open cavities not only provide structural stability but also simplify the fabrication process to a significant extent. The viability of this biosensor as a label-free biosensor has been evaluated using an antigen and an antibody from the Avian Influenza virus and DNA as the target biomolecules. The proposed analytical model and TCAD simulation results are in excellent agreement, demonstrating the reliability of the proposed device. Additionally, the biosensor’s sensitivity, which depends on cavity length, doping concentration, gate metal work function, and temperature variation, has been thoroughly explored. The gate-all-around structure, along with the integration of tri-step graded doping, GaN as the channel material, gate oxide stacking, and dual open cavity structure in the proposed biosensor, leads to significantly improved biosensing capabilities.

Insights into the design principles of JF-ED-VTFET for biosensing application

In this research article, we have designed a junction-free electrostatically doped vertical tunnel field-effect transistor (JF-ED-VTEFT) for label-free biosensing applications. We incorporated a nano-cavity within the gate-oxide layer near the source end of the FET to enable the detection of biomolecules based on the principle of dielectric modulation and without the requirement of external labeling. The proposed biosensor is thoroughly analyzed, considering various aspects such as electric field, energy band, transfer characteristics, and sensitivity parameters including energy band diagram, ON-current, ION/IOFF ratio, electrical analysis, and surface potential characteristics. The investigation of sensitivity encompasses practical challenges, such as different filling factors and step-profiles resulting from steric hindrance. In addition, the performance of the biosensor is evaluated by analyzing the temperature and scaling fluctuation in the integrated nanocavities. Additionally, values of biomolecules that are close to standard have been taken to validate the performance and provide insight into the sensitivity of the biosensor for detecting and analyzing the molecules.

Assessment of the Biosensing Capabilities of SiGe Heterojunction Negative Capacitance-Vertical Tunnel Field-Effect Transistor.

In this study, a comparison of the negative capacitance vertical tunnel field-effect transistor (NC-VTFET) and VTFET for biosensing applications was conducted. Dielectrically modulated TFET demonstrates better sensitivity than the traditional metal oxide field effect transistor as a biosensor in label-free biosensing applications. The TFET biosensor, however, has much room for advancement by enhancing its DC characteristics. This research addresses the impact of ferroelectric gate oxide for integration of negative capacitance (NC) effect with the SiGe heterojunction pocket at the source-channel junction to enhance performance for biosensor applications. By putting the NC layer over SiO2, the channel voltage increases with decreased subthreshold slope and OFF current, thereby creating an NC effect. Because SiGe has a narrow band gap, pocket doping of SiGe near the source channel junction will increase the concentration of charge carriers, improving the band-to-band tunneling. In order to aid in the integration of biomolecules and to modulate band-to-band tunneling based on charge density (qf), dielectric constant (k), temperature, and cavity length, a cavity is additionally inserted above the source channel junction and underneath the NC layer, near to SiO2. These values were compared with and without the incorporation of NC layer with respect to various electrical properties such as drain current (Id), sensitivity, and electric field (E). According to the findings, labeled and label-free biosensors' sensitivity may be increased by incorporating the NC effect into VTFET biosensors.

Performance optimization of epitaxial-layer based Si/SiGe hetero-junction area scaled tunnel FET label-free biosensors considering steric hindrance

This paper explores Si/SiGe hetero-junction dielectrically modulated area-scaled tunnel FET (DM-ASTFET) for label-free bio-sensing applications. The proposed sensor can detect bioanalytics such as protein, APTES, Choline Oxidase and Uricase. We have also investigated the influence of quantum confinement on the proposed device, and the onset voltage shifted by 0.1–0.3 V, as reported, without affecting the sensitivity mechanism. Sensitivity improvement is observed when the gate oxide length is 20 nm and the cavity length is 50 nm for a given bio-molecule due to the increased cross-section area for tunneling. The impact of epitaxial engineering on the biosensor's performance is also investigated in this work. A physics-based in-depth explanation of steric hindrance on the performance of the proposed sensor is also presented in this work. Finally, the optimum device design improves the sensitivity of ION ∼×103 and Vth ∼×2 times.

Physics based numerical model of a nanoscale dielectric modulated step graded germanium source biotube FET sensor: modelling and simulation

This paper proposes a novel dielectric modulated step-graded germanium source biotube FET for label-free biosensing applications. Its integrated structure and unique design combine the benefits of the gate stack, germanium source, triple-gate architecture, and a step-graded biotube channel, resulting in superior performance over existing biosensors. A compact two-dimensional analytical model for channel potential, drain current, threshold voltage, and subthreshold swing has been formulated and agrees well with the simulated results. The comprehensive investigation of different device parameters, including doping and bias, offers valuable insights into optimizing the biosensor’s performance. The proposed biosensor exhibits remarkable sensitivity, achieving up to 263 mV and 1495.52 nA for certain biomolecules, which has been validated by a compact analytical model and simulations performed on the SILVACO TCAD simulator. Several parameters are employed to assess the biosensor’s effectiveness: threshold voltage, ION/IOFF ratio, subthreshold swing, off-current, peak trans-conductance, and on-current. Furthermore, the biotube channel design enables lightweight and cost-efficient biosensors, enhancing the biosensor’s practicality. This work also includes an analysis of the effect of temperature on the biosensor’s performance and characteristics, providing insights into practical applications. High sensitivity of the biosensor signifies a significant advancement in biosensing technology, suggesting a wide range of potential applications in biomedical field.

Endurance Behavior of Z-Shaped Charge Plasma Tunnel FET for Biosensing Application

The tunneling field effect transistor (TFET) is a viable candidate for designing a highly sensitive biosensor. In this work, a doping-less Z-shaped dielectrically modulated charge plasma TFET (CPTFET) structure with misaligned cavity region on channel and source has been proposed for label-free biosensing applications. To design the device, charge plasma technique has been employed, where appropriate metal workfunction is used over intrinsic silicon to create n[Formula: see text] drain and p[Formula: see text]source regions. The charge plasma approach reduces thermal budget, random dopant fluctuation (RDF) and steps required for fabrication. The Z-shaped CPTFET includes the advantage of abrupt profile of doping at source-channel (tunneling) junction. Because cavities are created in source and gate oxide region, the abrupt doping profile suppresses ambipolar behavior and improves sensitivity. The performance of the proposed device for both charged and neutral biomolecules in terms of electric field, band energy, transfer characteristics, [Formula: see text] ratio and subthreshold swing (SS) has been examined. The response of other parameters like cavity thickness and cavity length on ON current has been analyzed using the Silvaco ATLAS device simulator.

From Self-Assembly of Colloidal Crystals toward Ordered Porous Layer Interferometry.

Interferometry-based, reflectometric, label-free biosensors have made significant progress in the analysis of molecular interactions after years of development. The design of interference substrates is a key research topic for these biosensors, and many studies have focused on porous films prepared by top-down methods such as porous silicon and anodic aluminum oxide. Lately, more research has been conducted on ordered porous layer interferometry (OPLI), which uses ordered porous colloidal crystal films as interference substrates. These films are made using self-assembly techniques, which is the bottom-up approach. They also offer several advantages for biosensing applications, such as budget cost, adjustable porosity, and high structural consistency. This review will briefly explain the fundamental components of self-assembled materials and thoroughly discuss various self-assembly techniques in depth. We will also summarize the latest studies that used the OPLI technique for label-free biosensing applications and divide them into several aspects for further discussion. Then, we will comprehensively evaluate the strengths and weaknesses of self-assembly techniques and discuss possible future research directions. Finally, we will outlook the upcoming challenges and opportunities for label-free biosensing using the OPLI technique.

A novel inverted T-shaped negative capacitance TFET for label-free biosensing application

The promising candidate for designing a highly sensitive biosensor is the negative capacitance tunneling field effect transistor (NCTFET). In this paper, to enhance the sensitivity and performance of the biosensor, we combined inverted T-shaped structure with NCTFET. We introduce negative capacitance effects by stacking ferroelectric materials on the gate dielectric layer. This paper presents a detailed comparative analysis of the proposed inverted T-shaped-NCTFET and TFET based biosensors for different dielectric constants and charge densities of the nano-cavity between the channel and source region locations of biosensor. Sensitivity has been measured in terms of drain current, on-state current, current switching ratio, electric field, and transconductance sensitivity. To establish a benchmark, the sensitivity of the proposed biosensor is also compared with the published literature in order to determine its effectiveness. It is conferred from the results that our biosensor can be a better alternative for the detection of the various neutral and charged biomolecules. All the device simulations are performed in a TCAD environment using a well-calibrated structure.

Sensitivity assessment of dielectric modulated GaN material based SOI-FinFET for label-free biosensing applications

Abstract This work presents the sensitivity assessment of gallium nitride (GaN) material-based silicon-on-insulator fin field effect transistor by dielectric modulation in the nanocavity gap for label-free biosensing applications. The significant deflection is observed on the electrical characteristics such as drain current, transconductance, surface potential, energy band profile, electric field, sub-threshold slope, and threshold voltage in the presence of biomolecules owing to GaN material. Further, the device sensitivity is evaluated to identify the effectiveness of the proposed biosensor and its capability to detect the biomolecules with high precision or accuracy. The higher sensitivity is observed for Gelatin (k = 12) in terms of on-current, threshold voltage, and switching ratio by 104.88%, 82.12%, and 119.73%, respectively. This work is performed using a powerful tool, three-dimensional (3D) Sentaurus Technology computer-aided design using a well-calibrated structure. The results pave the way for GaN-SOI-FinFET to be a viable candidate for label-free dielectric modulated biosensor applications.

Asymmetric tetramer metasurface sensor governed by quasi-bound states in the continuum

Abstract Asymmetric metasurfaces supporting quasi-bound states in the continuum (BICs) with high Q-factors and strong light–matter interaction properties are attractive platforms for label-free biosensing applications. Recently, various meta-atom geometries have been exploited to support sharp high-Q quasi-BIC resonance. However, which meta-atom design may be a better practical choice remains unclear. Here, we compared several established meta-atom designs to address this issue by conducting an extensive theoretical discussion on sensing capability and fabrication difficulty. We theoretically revealed that the tetramer meta-atom geometry produces a higher surface sensitivity and exhibits a larger size-to-wavelength ratio than other meta-atom schemes. Furthermore, we found that metasurfaces with a higher depth considerably enhance surface sensitivity. The performance of two asymmetric tetramer metasurfaces (ATMs) with different heights was demonstrated experimentally. Both shallow and thick ATM structures exhibit sharp high Q-factor resonances with polarization-insensitive features. Notably, the surface sensitivity is 1.62 times for thick ATM compared to that for shallow ones. The combination of properties opens new opportunities for developing biosensing or chemical-sensing applications with high performance.

High-sensitivity polarization-independent terahertz Taichi-like micro-ring sensors based on toroidal dipole resonance for concentration detection of Aβ protein

Abstract Terahertz (THz) metamaterial sensor is a newly-developing interdisciplinary technology, which combines the essential characteristics of THz spectroscopy and metamaterials, to obtain better sensitivity for trace detection of the different target analytes. Toroidal dipole resonances show great sensing potential due to their suppression of the radiative loss channel. Here, we found a high-quality planar toroidal dipole resonance in the breaking Chinese Taichi-like ring and then designed a novel polarization-independent terahertz toroidal sensor by combining four Taichi-like rings into a cycle unit. The sensor shows high-sensitivity sensing characteristics for the ultrathin analyte and refractive index. The optimized sensitivity of pure analytes under 4 μm coating thickness can numerically reach 258 GHz/RIU in the corresponding ∼1.345 THz frequency domain, which is much higher than that of previously reported sensors. We further fabricated experimentally the sensor and demonstrated its fascinating polarization-independent characteristics. Finally, it was successfully applied to the low-concentration detection (ranging from 0.0001 mg/mL to 10 mg/mL) of Aβ protein associated with Alzheimer’s disease. Our high-sensitivity polarization-independent THz toroidal dipole sensor would give access to rich applications in label-free biosensing.

A Fiber Bragg Grating Sensor Based on Cladding Mode Resonance for Label-Free Biosensing

A fiber-optic biosensing platform based on ultra-narrowband cladding mode resonances was developed on a high-reflectivity fiber Bragg grating (FBG) for targeting biomolecular detection. The multiple cladding modes with a high sensitivity to the refractive index (RI) were excited in the FBG by coupling between the forward-propagating guided core mode of the multimode fiber and the backward-propagating guided cladding mode of the FBG without any damage to the fiber structure or any change to the standard FBG manufacturing process. The full width at half maximum and the Q-factor of the typical cladding mode resonance operation of the proposed sensor are 80 pm and 19,270, respectively, which are better than those of most fiber-optic biosensors reported to date. In addition, the FBG sensor demonstrated a high sensitivity in protein detection and a high selectivity in serum sample assays. The sensitivity of this sensor was further increased simply by coating it with graphene oxide (GO) sheets on the sensing surface without using a signal amplification strategy. Furthermore, an ultra-low limit of detection (LOD) of 32 pM was obtained by the GO-coated FBG sensor for IgG detection. The proposed FBG sensor provides a competitive fiber-optic platform for biomolecular detection. It has a great potential for applications in label-free biosensing.

Performance Analysis of the Dielectrically Modulated Junction-Less Nanotube Field Effect Transistor for Biomolecule Detection.

The design of a high-performance Dielectrically Modulated Field Effect Transistor (DMFET) with smaller device dimension (channel length ≤ 100nm) has recently drawn significant research attention for point-of-care (POC) diagenesis applications. Driven by this paradigm, a Hetero-Gate Metal Dielectrically Modulated Junction-Less Nanotube Field Effect Transistor (DM-JLNFET) architecture is introduced and systematically investigated for label-free electrochemical biosensing application with the help of extensive numerical device simulations. The DM-JLNFET is carefully designed to exploit the advantages of superior gate control over channel electrostatics and electron injection component as well as strong immunity towards the short channel effects that lead to a notably high sensing performance compared to its conventional counterparts. In this context, the underlying physics of the transduction mechanism is analyzed in detail based on the device electrostatics and the carrier transport mechanism. The sensing performance of the proposed biosensor is quantified in terms of the drain current and threshold voltage sensitivities, which represents the relative modulations in these parameters with biomolecule conjugation. Typically, the DM-JLNFET exhibits a drain current and threshold voltage sensitivities as high as 1×10 12 and 0.70, respectively, for biomolecule dielectric constant above 2. Furthermore, the sensing performance demonstrates strong immunities towards non-uniform cavity occupancy. Finally, extensive comparative performance analysis with Dielectrically Modulated Nanowire Field Effect Transistor (DM-NWFET) is performed. The results exhibit that the proposed DM-JLNFET can offer more than 100% and eight orders of magnitude improvements in the threshold voltage and drain current sensitivities, respectively, for a range of small biomolecule dielectric constants.

Layer-by-layer coating of natural diatomite with silver nanoparticles for identification of circulating cancer protein biomarkers using SERS.

Surface-enhanced Raman scattering (SERS) is an emerging spectroscopy technique for detecting and characterizing chemical or biological structures in the vicinity of plasmonic nanostructures. Colloidal, solid, and flexible nanostructures are widely used in SERS experiments to enhance the Raman intensity. The nanostructure used in SERS is one of the main influencing parameters and a growing research area. Fabrication of simple and cheap SERS substrates with a high enhancement factor is desired. In this study, we fabricated a reproducible, cheap, and flexible SERS active strip by coating natural diatomite (biosilica) with silver nanoparticles (AgNPs) using the layer-by-layer assembly method and the fabricated strip is used for the label-free identification of circulating cancer protein biomarkers. SERS active strips were fabricated having different numbers of AgNP layers on natural diatomite and comprehensive characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV/vis absorption spectrophotometry were used. SERS activities of the strips depending on the number of layers were evaluated using 4-aminothiophenol (4-ATP) and rhodamine 6G (Rh6G) molecules. We found that the SERS intensity is strongly dependent on the number of AgNP layers, with the maximum SERS intensity obtained from the strip with 5 layers of AgNPs, having a 2.0 × 105 enhancement factor. The strip with the highest SERS activity was used for the label-free identification of circulating cancer protein biomarkers (HER2, CA15-3, PSA, MUC4, and CA27-29). The results demonstrate that the fabricated strip can help in the effective label-free identification of circulating protein biomarkers and open new directions for SERS-based label-free biosensing applications.

Smartphone-based dynamic measurements of electro-optically modulated lossy-mode resonance and its biosensing applications

In this work, we discuss an application of a smartphone-based spectrometer for dynamic analysis of optical response of an electro-optically modulated lossy-mode resonance (LMR) optical fiber sensor. The LMR was achieved when a section of a multimode optical fiber core was coated with a fluorine-doped tin oxide (FTO) thin film. The FTO, thanks to its electrical properties, has been simultaneously applied as an electrochemical electrode. It has been shown that when an electrical potential is applied to the obtained dual-domain sensor, the distribution of charge carriers in the FTO changes and it can be dynamically measured optically using the smartphone-based spectrometer with a time resolution below 0.5 s. Moreover, when charge carriers' accumulation is induced at the FTO surface, the changes on the sensor surface, such as biomaterial binding, can be identified with the device. The optical label-free biosensing performance of the system has been verified using streptavidin and green fluorescent protein (GFP) as receptor and target, respectively. The outcome of optical and electrical measurements, acquired simultaneously, were compared. It has been found that the system can detect concentration of GFP as low as 1 ng/mL. It must be noted that the smartphone-based dynamic optical measurements were possible with only the device, a low-cost detachable adapter, and a custom-made software application. Electrical measurements using a smartphone with such low-cost modifications are hardly possible. The setup can be further simplified using just a battery for setting the potential difference, thus establishing electro-optical modulation of the sensor. Such a system may be considered as suitable for a broad spectrum of sensors and their label-free biosensing applications.

Analysis and evaluation of Si(1-x) Ge(x) pocket on sensitivity of a dual-material double-gate dopingless tunnel FET label-free biosensor

This work reports a sensitivity analysis for a dual-material double-gate dopingless Tunnel FET (DM-DG-DLTFET) biosensor carrying a Si(1-x) Ge(x) pocket for improved performance of an overall device. The biomolecules are immobilized in a cavity suitable for small-sized biomolecules detection and the performance of the device is investigated by calculating the electrical properties altered due to the dielectric modulation caused by presence and absence of biomolecules by commercially available ATLASTM tool. The Si(1-x) Ge(x) pocket placed under the cavity at source-channel interface helps to attain better on-current which is usually less in case of other reported structures of Tunnel FETs. The variation in the composition of Ge is observed to obtain enhanced sensitivity. The device is studied for threshold voltage sensitivity of neutral as well as charged biomolecules and the nature of the present biomolecule is also determined using the transconductance-to-current ratio (gm/Ids) which can also be considered as a sensing metric. The optimized device design has been proposed keeping track of the electrical and physical trade-offs. Our results show a maximum of 539.5 mV shift in the threshold voltage when dielectric constant (K) of the neutral biomolecule is varied from 1 to 12 which makes our device evidently an efficient candidate for label-free biosensing application.

Sensitivity Enhancement of Group Refractive Index Biosensor through Ring-Down Interferograms of Microring Resonator.

In recent years, silicon-on-insulator substrates have been utilized for high-speed and low-power electronic components. Because of the high refractive index contrast of the silicon wire, its photonic device footprint can be significantly reduced. Moreover, the silicon photonic process is compatible with a complementary metal-oxide-semiconductor fabrication, which will benefit the high-density optoelectronic integrated circuits development. Researchers have recently proposed using the microring resonator (MRR) for label-free biosensing applications. The high-quality factor caused by the substantial electric field enhancement within the ring makes the MRR a good candidate for biomolecule detection under low analyte concentration conditions. This paper proposes an MRR chip to be a biosensor on the silicon platform through the relative displacement between the spatial ring-down interferograms at various cladding layers. The higher-order ring-down of the spatial interference wave packet will enhance the biosensing sensitivity after optimizing the coupling, MRR length, and the optical source bandwidth at the fixed optical waveguide loss. Finally, a typical sensitivity of 642,000 nm per refractive index unit is demonstrated under 0.1 μW minimum optical power detection for an MRR with a 100 μm radius. Higher sensitivity can be executed by a narrow bandwidth and lower silicon wire propagation loss.

Functional fluorine-doped tin oxide coating for opto-electrochemical label-free biosensors

Sensors operating in multiple domains, such as optical and electrochemical, offer properties making biosensing more effective than those working in a single domain. To combine such domains in one sensing device, materials offering a certain set of properties are required. Fluorine-doped tin oxide (FTO) thin film is discussed in this work as functional optically for guiding lossy modes and simultaneously electrochemically, i.e. as a conductive material for a working electrode. Performance of the FTO-based optical fiber lossy-mode resonance (LMR) sensor in both optical and electrochemical domains is analyzed. Additionally, to enhance applicability of the sensor, its probe-like reflection configuration has been developed. It is found that FTO may be considered as a promising alternative for other thin conductive oxides (TCO), such as indium tin oxide (ITO) that has been often applied up to date in various dual-domain sensing concepts. In the optical domain, the sensitivity of the FTO-LMR sensor to external refractive index (RI) has reached 450 nm/RIU in the RI range of 1.33–1.40 RIU. In the electrochemical domain, in turn, the response for FTO electrode in 1,1′-Ferrocenedimethanol solution has been reached with RedOx current low peak-to-peak separation. In contrast to the ITO-LMR sensors, the FTO-LMR counterparts exhibit a significant influence of applied potential on LMR wavelength shift in a wide potential range. It is shown using streptavidin as a target biomaterial that label-free biosensing applications of the FTO-LMR approach are possible. The dual-domain functionality allows for cross-verification between readouts received in both the domains, as well as enhancement of optical sensitivity when cross-domain interactions are applied.

Analytical modelling for surface potential of dual material gate overlapped-on-drain TFET(DM-DMG-TFET) for label-free biosensing application

This article presented the first-ever 2D analytical model for the surface potential of dual material gate overlapped-on-drain TFET (DMG-TFET) device for label-free biosensor application using dielectric modulation technique. The use of two different metal work functions for the gate (ϕM1<ϕM2) impacts the device’s surface potential to increase tunneling width at the secondary tunneling junction to enhance the device sensitivity compared to single material gate device. This model takes into account the effect of changing the dielectric constant value, location, and percentage of fill factor of the target biomolecules on the surface potential of the device. The parabolic approximation of surface potential is used for solving the 2D-Poisson’s equation by applying suitable boundary conditions. The analytical surface potential results are verified with the simulation result using the SILVACO Atlas tool.