Charged Biomolecules Research Articles

Study and analysis of a dielectric-modulated vertical tunnel FET biosensor using dual material gate

A bimetal gate heterogeneous dielectric vertical tunnel field-effect transistor (BG-HD-VTFET) biosensor has been investigated in this paper for the first time using engineered-gate concept, where nanogaps are introduced under tunnel gate (TG) to detect biomolecules near the device surface. To improve the detection performance of BG-HD-VTFET, an overlap is designed between source and pocket region, and the sensing ability of BG-HD-VTFET with and without overlap is compared in details. Further, an auxiliary gate (AG) is added for the proposed two devices to optimize the electrical characteristics, and the y composition of GaAsySb1-y in pocket region is optimized to enhance ON-state current, and then different neutral and charged biomolecules are considered to simulate device-level gate effects. In addition, the influence of different dielectric constant at fixed charge density is studied and the length of overlap is optimized. Simulation results show that the maximum sensitivity of BG-HD-VTFET with and without overlap can reach 3.3 × 103 and 1.9 × 103, respectively.

Sensitivity analysis of an inverted T-shaped vertical tunneling field effect transistor biosensor based on inserted finger type

This paper presents a biosensor based on a finger-inserted inverted T-shaped vertical tunneling field effect transistor (FP-T-TFET). In order to improve the sensitivity and performance of the biosensor, a finger-inserted contact between the source and the channel is used. A comparative analysis between the biosensor based on FP-T-TFET and conventional inverted T-shaped TFET (T-TFET) is simulated for the electrical properties and sensitivity of neutral biomolecules with different dielectric constants and charged biomolecules with different charge densities. The noise analysis of the proposed structure is also performed. Then, the effects of insertion finger distribution, cavity size and filling volume on the performance of FP-T-TFET are investigated. Finally, the structure was subjected to linear analysis, in which the pearson coefficient was 0.92, indicating that the structure has good linear correlation. The results show that the FP-T-TFET biosensor has higher sensitivity in detecting various neutral and charged biomolecules. All device simulations were performed in the TCAD environment with a well-calibrated structure.

Enhanced Biosensing with Double Gate Junctionless FET based on III–V Compound Semiconductor and Symmetric Cavity for Label-Free Detection of Neutral and Charged Biomolecules

Enhanced Biosensing with Double Gate Junctionless FET based on III–V Compound Semiconductor and Symmetric Cavity for Label-Free Detection of Neutral and Charged Biomolecules

Label-free biomolecule detection with dielectrically modulated double gate single cavity InGaAs/GaAsSb HTFET: Design considerations and performance evaluation

Dielectrically Modulated Double Gate Single Cavity InGaAs/GaAsSb HTFET (DMDG–SC–InGaAs/GaAsSb HTFET) is a novel label-free, nanocavity embedded dielectrically modulated heterostructure TFET-based biosensor. The III-V heterostructure (InGaAs/GaAsSb) has a high ION/IOFF ratio, better gate control, and higher tunnelling probability. In order to effectively reduce ambipolarity, asymmetrical doping is used at the p+ source and n+ drain, along with gate work function engineering. The stacked layers of HfO2/SiO2 gate oxide help to reduce the fringing electric field. The suggested device utilizes a dielectrically controlled technique to achieve biomolecule conjugation. This is done by etching a single nanogap cavity in the gate dielectric material towards the source end. An evaluation of the dielectric constants [K = 2.1, 2.63, 3.30, 6.3, and 12] of neutral and charged biomolecules compared to air [k = 1] is essential to determine the sensitivity of biosensors in an arid environment. The transconductance-to-current ratio (gm/Ids), switching ratio (ION/IOFF), and threshold voltage are the performance metrics used to evaluate the device sensitivity. The DM-DG–SC–InGaAs/GaAsSb HTFETpromises to be very sensitive while using less power during the detection process. It also shows that it could be a good choice for label-free biosensor applications.

Performance assessment of SiGe extended four corner source TFET for biosensing applications

In this paper, the performance of a novel SiGe extended four corner source tunneling field–effect transistor (SiGe EFCS TFET) based dielectrically modulated label-free biosensor has been investigated for biosensing applications. Using a combination of heterostructure (SiGe/Si) and extended four corner source (EFCS) lead to increased band–to–band tunneling (BTBT) probability, improved gate control and superior drain current sensitivity for biomolecule conjugation in comparison with a conventional TFET and Si EFCS TFET structures of similar dimensions. The influence of both the charge–neutral and charged biomolecules on the sensitivity performance is investigated using the Silvaco TCAD ATLAS semiconductor device simulator with a calibrated nonlocal BTBT model. Four different kinds of biomolecules such as Streptavidin, Ferro–cytochrome c, Keratin and Gelatin with various charge density values were used for this purpose. In order to model steric hindrance effects in partially filled cavities, in addition to various fill factors, four different step profile patterns have considered such as convex, concave, decreasing and increasing step profiles. Also, the dependence of the nanogap cavity properties on the sensing performance in terms of the length and thickness is investigated. A maximum drain current sensitivity of 1.69 × 105 is achieved in SiGe EFCS TFET for Gelatin biomolecules in a fully filled nanogap cavity at overdrive and drain voltages of 0.5 V.

Dielectric Modulated TFET on SELBOX Substrate as a Label-Free Biosensor Applications: Analytical Modeling Study and Sensitivity Analysis

Abstract The manuscript proposes a ferroelectric heterojunction TFET (BG-FE-HJ-STFET) on SELBOX substrates with a back gate to create an ultra-sensitive label-free biosensor with dielectric modulation for the detection of neutral and charged biomolecules. Within the proposed device, four cavities have been carved out for the biomolecules' immobilization under the front and rear gate dielectrics. By using a ferroelectric (FE) material as a gate stack, the low gate voltage is increased to be more effective by causing a negative capacitance phenomenon. The response of the proposed biosensor to four impartial biomolecules with different dielectric constants Protein (k=8), Biotin (k=2.63), 3-Aminopropyl-triethoxysilane (APTES) (k=3.57), and Streptavidin (k=0.1) has been investigated. Deoxyribonucleic acid (DNA), a charged biomolecule, is also examined for dielectric constant of k=6 with respect to both charges (Negative and Positive)) densities. The device is simulated with the commercially available SILVACO ATLASTM TCAD tool. The performance analysis relies on several figures of merit (FOMs) such as DC/RF and sensitivity (including drain current, ION/IOFF ratio, and subthreshold swing) for both neutral and charged biomolecules. The optimized cavity structure demonstrates a notable sensitivity in drain current (2.7x108) and a significant ION/IOFF sensitivity (1.42x1011). One of the main problems with current biosensors is the difficulty and expense of production in the nanoscale realm.

Implicit Solvent with Explicit Ions Generalized Born Model in Molecular Dynamics: Application to DNA.

The ion atmosphere surrounding highly charged biomolecules, such as nucleic acids, is crucial for their dynamics, structure, and interactions. Here, we develop an approach for the explicit treatment of ions within an implicit solvent framework suitable for atomistic simulations of biomolecules. The proposed implicit solvent/explicit ions model, GBION, is based on a modified generalized Born (GB) model; it includes separate, modified GB terms for solute-ion and ion-ion interactions. The model is implemented in the AMBER package (version 24), and its performance is thoroughly investigated in atomistic molecular dynamics (MD) simulations of double-stranded DNA on a microsecond time scale. The aggregate characteristics of monovalent (Na+ and K+) and trivalent (Cobalt Hexammine, CoHex3+) counterion distributions around double-stranded DNA predicted by the model are in reasonable agreement with the experiment (where available), all-atom explicit water MD simulations, and the expectation from the Manning condensation theory. The radial distributions of monovalent cations around DNA are reasonably close to the ones obtained using the explicit water model: expressed in units of energy, the maximum deviations of local ion concentrations from the explicit solvent reference are within 1 kBT, comparable to the corresponding deviations expected between different established explicit water models. The proposed GBION model is able to simulate DNA fragments in a large volume of solvent with explicit ions with little additional computational overhead compared with the fully implicit GB treatment of ions. Ions simulated using the developed model explore conformational space at least 2 orders of magnitude faster than in the explicit solvent. These advantages allowed us to observe and explore an unexpected "stacking" mode of DNA condensation in the presence of trivalent counterions (CoHex3+) that was revealed by recent experiments.

Design of a novel high-sensitive SOI-Junctionless BioFET overcoming sensitivity degradation problems

For the first time, a new configuration of label-free junctionless semiconductor device is proposed to boost sensitivity in the identification of biomolecule specifies. Instead of creating the nanocavity inside the gate oxide, the nanocavity is created in the channel region which is very useful for the SOI junctionless technology based biodevice having a high current in all operating modes. For better control of the conduction mechanism, a hole trench is created under the channel region just inside the buried oxide. This will help to modulate the energy bands terminating in enhancing the sensing performance. Unlike the conventional biosensors needing a large-scale gate oxide thickness for trapping the biomolecules, the proposed biosensor can work for very low gate oxide thickness. The different biomolecules such as Biotin, Protein A, Bacteriophage T7, and Apomyoglobin have been utilized as targeted biomolecules for evaluating the sensitivity. Comparing the proposed biosensor with the conventional and other biosensors showed an enhanced sensing performance. Practical related issues during the process of sensing in terms of fill factor percentage, steric hindrance of biomolecules, and the charges of biomolecules have been focused in the recommended biodevice. All the results exhibited high superiority of performance of the suggested biodevice as compared to the conventional biosensor.

Parallel Brownian dynamics implementation of the Angular Averaged Ewald sums in Coulombic fluids

In nature, Coulombic fluids are present in many different forms, for instance, as aqueous electrolytes dissolving charged biomolecules (such as the DNA or lipid bilayers), macroion or nanoparticle solutions, molten salts, ionic liquids, plasmas, etc. One important characteristic of charged fluids is the long-range electrostatic interaction, which must be incorporated adequately in computer simulations in order to avoid artifacts. In this work, an MPI-Fortran 90 parallel implementation of Coulombic interactions using the Angular Averaged Ewald sums in Brownian dynamics is reported. This computational implementation is considerably faster than the corresponding serial version for a small to a sizable number of particles (tens of thousands). The accuracy of the parallelized Angular Averaged Ewald sums is compared regarding the Ewald sums method at the level of structural and electrostatic properties of a size- and valence-asymmetric electrolyte.

Design and sensitivity analysis of a vertical TFET with dielectric pocket for its use as label free biosensor

A comprehensive analysis of a dielectrically modulated vertical tunnel field effect transistor (VTFET) as a label free biosensor is presented in this article. The proposed structure considers an n+ pocket at the source /channel interface and a dielectric pocket at channel/drain interface. The sensitivity of the VTFET biosensor has been investigated, introducing neutral and charged biomolecules of different dielectric constants at the nanogap cavity. The n+ doped pocket introduced at the source/channel junction improves the output characteristics of the proposed VTFET due to its conduction mechanism in both lateral and vertical directions, thereby improving the sensitivity of VTFET biosensor as well. The proposed VTFET biosensor gains the sensitivity in the order of 105 for a fully filled cavity. Moreover, the HfO2 dielectric pocket at the channel/drain interface suppresses the deteriorating ambipolar behaviour and also enhances the ambipolar current sensitivity compared to a VTFET biosensor without dielectric pocket. Thus, it is perceived that the main drawback of TFET, ambipolar nature, has evolved as an advantage for sensing applications. The VTFET biosensor has been analyzed with regards to variations in dielectric constant of cavity, density of charge, length and height of cavity, mole fraction and also operating temperature at a particular bias condition to judge its sensing capability. A status map has been presented where the proposed VTFET biosensor has been compared with some of the significant works reported in literature in terms of sensitivity and selectivity.

Gadolinium-Based NMR Spin Relaxation Measurements of Near-Surface Electrostatic Potentials of Biomolecules.

NMR spectroscopy is an important tool for the measurement of the electrostatic properties of biomolecules. To this point, paramagnetic relaxation enhancements (PREs) of 1H nuclei arising from nitroxide cosolutes in biomolecular solutions have been used to measure effective near-surface electrostatic potentials (ϕENS) of proteins and nucleic acids. Here, we present a gadolinium (Gd)-based NMR method, exploiting Gd chelates with different net charges, for measuring ϕENS values and demonstrate its utility through applications to a number of biomolecular systems. The use of Gd-based cosolutes offers several advantages over nitroxides for ϕENS measurements. First, unlike nitroxide compounds, Gd chelates enable electrostatic potential measurements on oxidation-sensitive proteins that require reducing agents. Second, the large electron spin quantum number of Gd (7/2) results in notably larger PREs for Gd chelates when used at the same concentrations as nitroxide radicals. Thus, it is possible to measure ϕENS values exclusively from + and - charged compounds even for highly charged biomolecules, avoiding the use of neutral cosolutes that, as we further establish here, limits the accuracy of the measured electrostatic potentials. In addition, the smaller concentrations of cosolutes required minimize potential binding to sites on macromolecules. Fourth, the closer proximity of the paramagnetic center and charged groups within Gd chelates, in comparison to the corresponding nitroxide compounds, enables more accurate predictions of ϕENS potentials for cross-validation of the experimental results. The Gd-based method described here, thus, broadens the applicability of studies of biomolecular electrostatics using solution NMR spectroscopy.

Threshold voltage model development of N+ pocket vertical junctionless TFET (V-JL-TFET) as a label free biosensor

This work investigates into the potential application of an improved N+ pocket Vertical Junctionless TFET (V-JL-TFET) as a label free biosensor. To calculate the sensitivity of the biosensor, an analytical model based on device physics was developed that accounts for the impact of both charged and uncharged biomolecules on the threshold voltage (Vth). As a result, the developed model offers a solution that is applicable for both uncharged and charged biomolecules. This model demonstrates a strong agreement with the experimentally determined threshold voltage (Vth) obtained from simulation results. Furthermore, sensitivity is obtained by assessing the shift in threshold voltage (Vth) resulting from changes in the dielectric constant. It's observed that Vth increases with decrease in dielectric value. The Vth value with empty nanogaps has been used as a reference point. Finally, the sensitivity of gate threshold voltage was calculated, and the obtained values are high enough to detect both charged and uncharged biomolecules. A detailed analysis of Selectivity, Linearity, stability and reliability of the proposed Biosensor is also presented.

Layered Double Hydroxides (LDH) as Delivery Vehicles of a Chimeric Protein Carrying Epitopes from the Porcine Reproductive and Respiratory Syndrome Virus.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes reproductive failure and respiratory symptoms, leading to huge economic losses for the pig farming industry. Although several vaccines against PRRSV are available in the market; they show an overall low efficacy, and several countries have the need for vaccines covering the local, circulating variants. This project aims at developing a new chimeric antigen targeting specific epitopes from PRRSV and evaluating two test adjuvants to formulate a vaccine candidate. The test antigen was called LTB-PRRSV, which was produced recombinantly in Escherichia coli and consisted of the heat labile enterotoxin B subunit from E. coli (LTB) and four epitopes from PRRSV. LTB-PRRSV was rescued as inclusion bodies and methods for its solubilization, IMAC-based purification, and refolding were standardized, leading to mean yields of 18 mg of pure protein per liter culture. Layered double hydroxides (LDH) have been used as vaccine adjuvants given their biocompatibility, low cost, and positive surface charge that allows an efficient adsorption of negatively charged biomolecules. Therefore, LDH were selected as delivery vehicles of LTB-PRRSV. Pure LTB-PRRSV was adsorbed onto LDH by incubation at different LDH:LTB-PRRSV mass ratios (1:0.25, 1:0.5, 1:1, and 1:2) and at pH 9.5. The best adsorption occurred with a 1:2 mass ratio, and in a sucrose-tween solution. The conjugates obtained had a polydispersity index of 0.26, a hydrodynamic diameter of 192 nm, and a final antigen concentration of 64.2 μg/mL. An immunogenicity assessment was performed by injecting mice with LDH:LTB-PRRSV, Alum/LTB-PRRSV, or LTB-PRRSV in a scheme comprising three immunizations at two-week intervals and two dose levels (1 and 5 μg). LTB-PRRSV was capable of inducing strong humoral responses, which lasted for a longer period when LDH was used as the delivery vehicle/adjuvant. The potential of LDH to serve as an attractive carrier for veterinary vaccines is discussed.

Sensitivity analysis of bi-metal stacked-gate-oxide hetero-juncture tunnel fet with Si0.6Ge0.4 source biosensor considering non-ideal factors.

This article provides insights in designing a dielectrically modulated biosensor by adopting high-k stacked gate oxide proposition in a bi-metal hetero-juncture Tunnel Field Effect Transistor (BM-SO-HTFET) with Si0.6Ge0.4 source. The integrated effect of heterojunction and stacked gate oxide leads to enhanced electrical performance of the proposed device in terms of carrier mobility and suppressed leakage current. Nano-cavity engraved beneath the bi-metal gate structure across the source/channel end acts the binding site of the biomolecules to be detected. This Configuration leads to improved control of biomolecules over source/channel tunnelling rate and the same is reflected in the sensing ability of the device while extracting the ON current sensitivity (SON) of the sensor. The reported biosensor is simulated using Silvaco ATLAS calibrated simulation framework. The analysis of the device sensitivity is carried out varying dielectric constants (k) of various biomolecules, both neutral as well as charged. Our study reveals that BM-SO-HTFET with Ge mole fraction composition x = 0.4 exhibits sensitivity as high as 4.1 × 1010 for neutral biomolecules and 3.2 × 1011 for positively charged biomolecules with k = 12. Furthermore, a transient response profile for the drain current with various biomolecules is explored to determine the varying settling time. From the simulation results, it is noted that BM-SO-HTFET exhibits ON current sensitivity of 4.1 × 1010 and 3.2 × 1011 for neutral and charged biomolecules respectively. In addition to this, for highly sensitive and real time detection of biomolecules, the impact of temperature and certain non-ideal factors drifting from ideal case of fully filled cavity have also been considered to analyze its optimum sensing performance.

Raised Ge-Source with n+ pocket and recessed drain line TFET: A proposal for biosensing applications

In this paper, we present a novel raised Ge-source with an n+ pocket and recessed drain line Tunnel Field-Effect Transistor (TFET). It offers enhanced performance for potential biosensing applications. The proposed device comprises a Ge source with a low bandgap, an n+ pocket, and a larger tunneling area. This results in improved performance characteristics: an ON current of 54.27 μA/μm, an ON-current to OFF-current ratio of 1.5 × 1012, and an average subthreshold swing of 21.3 mV/dec. The recessed drain design eliminates ambipolarity, further enhancing performance. The study thoroughly investigates biosensing capabilities, including DC and transient analyses, evaluating charged and neutral biomolecules (uricase, biotin, 3-aminopropyltriethoxysilane, DNA, keratin, and gelatin). The proposed biosensor, with a higher drain current sensitivity of 1.2 × 109 for gelatin (k = 12) and 3.05 × 108 for keratin (k = 8), outperforms existing approaches, making our proposed biosensor a compelling choice for future low-power biomedical applications.

Quantum sensing of microRNAs with nitrogen-vacancy centers in diamond

Label-free detection of nucleic acids such as microRNAs holds great potential for early diagnostics of various types of cancers. Measuring intrinsic biomolecular charge using methods based on field effect has been a promising way to accomplish label-free detection. However, the charges of biomolecules are screened by counter ions in solutions over a short distance (Debye length), thereby limiting the sensitivity of these methods. Here, we measure the intrinsic magnetic noise of paramagnetic counter ions, such as Mn2+, interacting with microRNAs using nitrogen-vacancy (NV) centers in diamond. All-atom molecular dynamics simulations show that microRNA interacts with the diamond surface resulting in excess accumulation of Mn ions and stronger magnetic noise. We confirm this prediction by observing an increase in spin relaxation contrast of the NV centers, indicating higher Mn2+ local concentration. This opens new possibilities for next-generation quantum sensing of charged biomolecules, overcoming limitations due to the Debye screening.

Design and Simulation of Dielectrically Modulated Dual Material Gate-Stack Double-Gate FinFET Biosensor

This study developed and evaluated a dual-material gate stack double-gate FinFET-based biosensor (DM-GS-DG FinFET). The device was dielectrically modulated and investigated for molecules, such as streptavidin, gluten, zein, hen egg-white lysozyme, and acetylene tetrabromide, based on current, threshold voltage, subthreshold swing, and switching sensitivity. The influence of charged and neutral biomolecules within the nanocavity on the electric, analog, and radiofrequency parameters was recorded. This study was conducted relative to different dielectric κ-values of 12 in terms of the percentage sensitivity improvement (SI%). The results reveal that the percentage of sensitivity ION improves effectively, especially for low κ-values, compared with other sensitivity measures. All the sensitivity evaluations indicated that DM-GS-DG-FinFET combined with biomolecules is a viable option for biosensing purposes.

Electrospray-assisted cryo-EM sample preparation to mitigate interfacial effects.

Addressing interfacial effects during specimen preparation in cryogenic electron microscopy remains challenging. Here we introduce ESI-cryoPrep, a specimen preparation method based on electrospray ionization in native mass spectrometry, designed to alleviate issues associated with protein denaturation or preferred orientation induced by macromolecule adsorption at interfaces. Through fine-tuning spraying parameters, we optimized protein integrity preservation and achieved the desired ice thickness for analyzing target macromolecules. With ESI-cryoPrep, we prepared high-quality cryo-specimens of five proteins and obtained three-dimensional reconstructions at near-atomic resolution. Our findings demonstrate that ESI-cryoPrep effectively confines macromolecules within the middle of the thin layer of amorphous ice, facilitating the preparation of blotting-free vitreous samples. The protective mechanism, characterized by the uneven distribution of charged biomolecules of varying sizes within charged droplets, prevents the adsorption of target biomolecules at air-water or graphene-water interfaces, thereby avoiding structural damage to the protein particles or the introduction of dominant orientation issues.

Sensitivity estimation of biosensor in a tapered cavity MOSHEMT

The present research provides a comprehensive investigation of the structural modification at the cavity under the gate (CUG) on the metal oxide semiconductor high electron mobility transistor (MOSHEMT)-based biosensor by projecting its basic figures of merit (FOMs). The effect of a tapering dielectric on the sensitivity of the biosensor has not been extensively investigated in many research efforts. Therefore, to account for the larger binding surface, the current study considers a wide range of permittivity of the biomolecules from 1 to 10, using the dielectric modulation technique in the tapered cavity. Various cavities are analysed to enhance the sensitivity. The findings indicate that the presence of biomolecules causes a considerable fluctuation in the drain current, threshold voltage, on-current, off-current, channel potential, and oxide capacitance. It has also been estimated how various fill percentages and charged and neutral biomolecules affect the device’s sensitivity. The tapered dielectric MOSHEMT offered an on-current sensitivity and threshold voltage sensitivity of 1.25 and 0.889 for neutral biomolecule (k = 8) and 0.562 and 2.23 for positively charged biomolecule respectively. Thus, tapering of the oxide does offer better sensitivities that can be exploited for biosensing applications.

Ferroelectric Bi2O2Te-Based Plasmonic Biosensor for Ultrasensitive Biomolecular Detection.

Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi2O2Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi2O2Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1fm is achieved for protein molecules and an unprecedented 0.1fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range.