Label-free Detection Of Biomolecules Research Articles

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.

Split Gate Bulk-Planar Junctionless FET-Based Biosensor for Label-Free Detection of Biomolecules

Split Gate Bulk-Planar Junctionless FET-Based Biosensor for Label-Free Detection of Biomolecules

Label-Free Biosensor Based on Particle Plasmon Resonance Coupled with Diffraction Grating Waveguide.

Particle plasmon resonance (PPR), or localized surface plasmon resonance (LSPR), utilizes intrinsic resonance in metal nanoparticles for sensor fabrication. While diffraction grating waveguides monitor bioaffinity adsorption with out-of-plane illumination, integrating them with PPR for biomolecular detection schemes remains underexplored. This study introduces a label-free biosensing platform integrating PPR with a diffraction grating waveguide. Gold nanoparticles are immobilized on a glass slide in contact with a sample, while a UV-assisted embossed diffraction grating is positioned opposite. The setup utilizes diffraction in reflection to detect changes in the environment's refractive index, indicating biomolecular binding at the gold nanoparticle surface. The positional shift of the diffracted beam, measured with varying refractive indices of sucrose solutions, shows a sensitivity of 0.97 mm/RIU at 8 cm from a position-sensitive detector, highlighting enhanced sensitivity due to PPR-diffraction coupling near the gold nanoparticle surface. Furthermore, the sensor achieved a resolution of 3.1 × 10-4 refractive index unit and a detection limit of 4.4 pM for detection of anti-DNP. The sensitivity of the diffracted spot was confirmed using finite element method (FEM) simulations in COMSOL Multiphysics. This study presents a significant advancement in biosensing technology, offering practical solutions for sensitive, rapid, and label-free biomolecule detection.

A P+ pocket doped 4H–SiC Schottky barrier FET as highly sensitive label-free biosensor

In this paper, a 4H–SiC Schottky barrier field-effect transistor with a P+ doping Pocket based on dielectric modulation effect for label-free detection of biomolecules has been proposed. Upon optimization of the length and position of P+ doping pocket, the sensitivity of the biosensor achieves the maximum when it is located within the channel 1 nm away from the Schottky contact with a length of 5 nm. Simulations have been performed for different dielectric constants and biomolecules with different charge densities by Sentaurus TCAD. The results show that the new structure has an on-current sensitivity of 1.03 × 108, a maximum transconductance sensitivity of 6.24 × 107, a threshold voltage sensitivity of 65 mV, and an Ion/Ioff ratio sensitivity of 1.8 × 104 for neutral biomolecules with K = 12. In addition, the fill factor of the cavity and linearity of the proposed structure are considered in this paper. Further, the on-current sensitivity of our proposed structure is gauged against state of the art, which demonstrate a high sensitivity of our proposed biosensors. The smaller size and prominent sensitivity characteristics of the biosensor proposed in this paper have made it widely used in the field of biomedical detection that requires high integration and efficient detection.

Advances in Label-Free Glucose Detection Using Self-Assembled Nanoparticles and Surface-Enhanced Raman Spectroscopy.

In the landscape of biomolecular detection, surface-enhanced Raman spectroscopy (SERS) confronts notable obstacles, particularly in the label-free detection of biomolecules, with glucose and other sugars presenting a quintessential challenge. This study heralds the development of a pioneering SERS substrate, ingeniously engineered through the self-assembly of nanoparticles of diverse sizes (Ag1@Ag2NPs). This configuration strategically induces 'hot spots' within the interstices of nanoparticles, markedly amplifying the detection signal. Rigorous experimental investigations affirm the platform's rapidity, precision, and reproducibility, and the detection limit of this detection method is calculated to be 6.62 pM. Crucially, this methodology facilitates nondestructive glucose detection in simulated samples, including phosphate-buffered saline and urine. Integrating machine learning algorithms with simulated serum samples, the approach adeptly discriminates between hypoglycemic, normoglycemic, and hyperglycemic states. Moreover, the platform's versatility extends to the detection and differentiation of monosaccharides, disaccharides, and methylated glycosides, underscoring its universality and specificity. Comparative Raman spectroscopic analysis of various carbohydrate structures elucidates the unique SERS characteristics pertinent to these molecules. This research signifies a major advance in nonchemical, label-free glucose determination with enhanced sensitivity via SERS, laying a new foundation for its application in precision medicine and advancing structural analysis in the sugar domain.

A high Q-factor evanescent field fiber sensor coated with C-MWCNT for label-free HPV determination

A high Q-factor evanescent field fiber sensor is designed based on a fiber Bragg grating (FBG) coated with carboxylic multi-walled carbon nanotubes (C-MWCNT). In a high-reflectivity FBG, multiple cladding modes are stimulated as the forward-moving guided mode within the core of the multimode fiber is coupled to the FBG’s reverse-moving guided mode within the cladding. Our evanescent field fiber sensor is highly sensitive to the refractive index without altering the architecture of fiber or deviating from the conventional process of fabricating fiber gratings. The proposed sensor exhibits a full-width at half maximum (FWHM) of 78 pm and a Q-factor of 1.9 × 104 for its standard cladding-mode resonance, outperforming the majority of reported evanescent field fiber sensors in these parameters. Furthermore, by coating C-MWCNT on the fiber sensing surface, our sensor has been demonstrated to combine multiple functions into one, such as label-free determination of human papilloma virus (HPV) DNA sequences, the measurement of different concentrations, and mispairing discrimination. The sensor design put forward offers a compelling technique within the realm of optical fiber sensing for refractive index and label-free biomolecule detection.

Simulation and modeling of high-sensitive JL-TFET based biosensor for label free detection of biomolecules

Simulation and modeling of high-sensitive JL-TFET based biosensor for label free detection of biomolecules

Trench Dual Gate Junctionless Field Effect Transistor

Diversified biomolecules sensing is turning out to be the most promising area of research due to ever decreasing healthy lifestyle. Field effect transistorized biosensing approach puts its signature as label free, portable and also very careful pathway. In this present work a trench structured dielectric modulated double gate junction-less field effect transistor (TG-DMJLFET) is urbanized using SILVACO ATLAS simulator for label free detection of biomolecules. The developed structure has two vertically positioned gates in distinct trenches. For immobilizing biomolecules, two cavities are formed in the gate oxide region for dielectric modulation. The dielectric constant (k) has been varied over a wide range of 1.54 (Uricase) to 12(Gelatin) signifying the sensing of diverse charged biomolecules. The sensitivity is evaluated in terms of threshold voltage shift and transconductance . The in-depth electrostatic analysis is illustrated in terms of central potential ,energy band diagram ,drive current and also by the depiction of the electric field .In case of charged biomolecules, the shift in threshold voltage is obtained as 350 mV for change in the di-electric constant (k) ranging from 1.54 to 12. The transconductance alteration is observed as 1.94×10-5 when the k is changed from 3.46 to 12 .The device has showed excellent performance in biomolecules sensing.

Label-free detection of biomolecules using inductively coupled plasma mass spectrometry (ICP-MS).

Bioassays using inductively coupled plasma mass spectrometry (ICP-MS) have gained increasing attention because of the high sensitivity of ICP-MS and the various strategies of labeling biomolecules with detectable metal tags. The classic strategy to tag the target biomolecules is through direct antibody-antigen interaction and DNA hybridization, and requires the separation of the bound from the unbound tags. Label-free ICP-MS techniques for biomolecular assays do not require direct labeling: they generate detectable metal ions indirectly from specific biomolecular reactions, such as enzymatic cleavage. Here, we highlight the development of three main strategies of label-free ICP-MS assays for biomolecules: (1) enzymatic cleavage of metal-labeled substrates, (2) release of immobilized metal ions from the DNA backbone, and (3) nucleic acid amplification-assisted aggregation and release of metal tags to achieve amplified detection. We briefly describe the fundamental basis of these label-free ICP-MS assays and discuss the benefits and drawbacks of various designs. Future research is needed to reduce non-specific adsorption and minimize background and interference. Analytical innovations are also required to confront challenges faced by in vivo applications.

Dielectric Modulated Charge Plasma-Based Label Free Detection of Biomolecules in Dual Metal DG TFET Biosensors

Dielectric Modulated Charge Plasma-Based Label Free Detection of Biomolecules in Dual Metal DG TFET Biosensors

Gate Engineered Ferroelectric Junctionless BioFET for Label-Free Detection of Biomolecules

Gate Engineered Ferroelectric Junctionless BioFET for Label-Free Detection of Biomolecules

Gold Nanorod Density-Dependent Label-Free Bacteria Sensing on a Flake-like 3D Graphene-Based Device by SERS.

Surface-enhanced Raman spectroscopy (SERS) is an effective technique for biosensing, enabling label-free detection of biomolecules with enhanced sensitivity. There is a tremendous probability of signal failure in Raman frequencies because of the scattering of the Raman radiation in liquids, effective SERS improvement is required to reduce this issue when considering liquid specimens. We examined a liquid bacterial sample, investigating the electrostatic interactions of the bacterial samples with gold nanorods (AuNRs) and graphene. We established a voltage-gated 3D graphene functionalized with an AuNR-based device on the silicon substrate for SERS measurements when the applied voltage ranges from 0 to 3 V. Moreover, AuNRs density-susceptible bacterial sample analysis with varied concentrations of bacterial samples has also been described. Using bacterial SERS analysis, the bacterial components amide II (1555-1565 cm-1) and amide III (1250-1350 cm-1) have been discovered for both bacteria, Gram-positive, Listeria monocytogenes and Gram-negative, Salmonella typhi. Our fabricated device affords an interesting label-free, rapid, and reproducible bacterial sample analysis based on the density of the AuNRs when functionalizing flake-like 3D graphene, which can help facilitate label-free bacteria sensing platforms.

A single gate Si1−xGex dopingless TFET functioned as an effective label-free biosensor

This paper examines the sensitivity of a newly presented heterojunction dopingless tunnel field effect transistor (HJ-DLTFET) biosensor for the label-free detection of biomolecules. The etched nanocavity is introduced in the source metal region for better sensing ability. The dielectric constants (k) of five neutral biomolecules are employed in this paper to test the sensitivity of the proposed biosensor. The electrostatic performance is investigated based on transfer characteristics, energy band, tunneling distance (λ) at source/channel (S/C) interface, drain current (ID) variation for different dielectric constant (k), drain to source voltage (VDS) variation and mole fraction (x) variation respectively. Further, the RF performance analysis includes gate/source capacitance (Cgs), total gate capacitance (Cgg), cut-off frequency (ft), and maximum frequency (fm) analysis. Similarly, sensitivity analysis consists of current sensitivity (SID), current ratio sensitivity (Sratio), average SS sensitivity (SSS), Cgs sensitivity, Cgg sensitivity, ft sensitivity, and fm sensitivity. The investigation is carried out with the variation of neutral biomolecules in terms of various k inside the cavity. Similarly, the impact of charged biomolecules on the sensitivity of the proposed biosensor is investigated. The HJ-DLTFET sensor provides the maximum sensitivity SID of 1.56 × 1010, Sratio of 5.95 × 109, and SSS of 0.80 for Gelatin (k = 12.00) at room temperature using the Silvaco TCAD simulation tool. Combining a low band gap Si0.6Ge0.4 source with a high band gap silicon channel and a high-k (HfO2) improves drain current sensitivity without impacting leakage current.

Electrokinetic Active Particles for Motion-Based Biomolecule Detection.

Detection of biomolecules is essential for patient diagnosis, disease management, and numerous other applications. Recently, nano- and microparticle-based detection has been explored for improving traditional assays by reducing required sample volumes and assay times as well as enhancing tunability. Among these approaches, active particle-based assays that couple particle motion to biomolecule concentration expand assay accessibility through simplified signal outputs. However, most of these approaches require secondary labeling, which complicates workflows and introduces additional points of error. Here, we show a proof-of-concept for a label-free, motion-based biomolecule detection system using electrokinetic active particles. We prepare induced-charge electrophoretic microsensors (ICEMs) for the capture of two model biomolecules, streptavidin and ovalbumin, and show that the specific capture of the biomolecules leads to direct signal transduction through ICEM speed suppression at concentrations as low as 0.1 nM. This work lays the foundation for a new paradigm of rapid, simple, and label-free biomolecule detection using active particles.

Universal Method for Label-Free Detection of Pathogens and Biomolecules by Surface-Enhanced Raman Spectroscopy Based on Gold Nanoparticles.

The detection of biomolecules is the key to basic molecular research, diagnostics, drug screening, and other biomedical applications. However, the existing detection techniques can only detect single classes of biomolecules, which warrant the development of a versatile biomolecule detection platform. Here, we developed a universal method for label-free detection of biomolecules via surface-enhanced Raman spectroscopy (SERS) by using sulfhydryl-modified gold nanoparticles as the substrate. The biomolecules can be adsorbed on the surface of gold nanoparticles cleaned by bromide ions to obtain initially enhanced Raman signals, and the aggregator (calcium ion) was further added to form a "hot spot", which enhanced the biomolecular signal again. Through the "two-step enhancement method", we were able to obtain fingerprints of DNA, RNA, amino acids, peptides, proteins, viruses, bacteria, and lipid molecules. This low-toxic, highly sensitive, and widely applicable technique has potential applications in biomedical research, clinical testing, and disease diagnosis and lays the foundation for the development of SERS technology in various fields.

Dual Cavity Dielectric Modulated Ferroelectric Charge Plasma Tunnel FET as Biosensor: For Enhanced Sensitivity.

This work reports a biosensor based on the dual cavity dielectric modulated ferroelectric charge plasma Tunnel FET (FE-CP-TFET) with enhanced sensitivity. By incorporating underlap and dielectric modulation phenomena, ultra sensitive, and label-free detection of biomolecules is achieved. The cavity is carved underneath the source-gate dielectric for the immobilization of the biomolecules. The ferroelectric (FE) material is used as a gate stack to realize a negative capacitance effect to amplify the low gate voltage. To avoid the issues with metallurgical doping such as random dopant fluctuations (RDFs), ambipolar conduction, and increased thermal budget, the charge plasma concept is deployed. Based on our exhaustive ATLAS 2D TCAD study, the electric field, hole concentration, and energy band diagram of the proposed device are critically analyzed to provide a better insight into the biosensor working mechanism. Here, two different figures-of merits (FOMs) for the proposed biosensor are investigated such as sensitivity and linearity. Sensitivity has been measured in terms of drain current, [Formula: see text] to [Formula: see text] ratio, electric field, and transconductance sensitivity. Linearity analysis of the proposed structure includes [Formula: see text] ratio. The reported biosensor is capable of detecting several biomolecules such as (neutral and charged as well) Streptavidin (2.1), 3-aminopropyltriethoxysilane (APTES) (K =3.57 ), Keratin (K =8 ), T7 (K =6.3 ) and Gelatin (K =12 ). It was observed that the optimized cavity structure demonstrates high drain current sensitivity ( 2.7×108 ) as well as high [Formula: see text] sensitivity ( 1.45×108 ). Further, the linearity analysis shows that the Pearson's coefficient of both structures have been achieved as ( r2 ≥ 0.8 ). It is conferred from the results that our biosensor can be a better alternative for the detection of the various neutral and charged biomolecules.

Dielectric Modulated Nanotube Tunnel Field-Effect Transistor as a Label Free Biosensor: Proposal and Investigation.

Dielectric modulated (DM) field-effect transistors (FET) have gained significant popularity for label-free detection of biomolecules. However, the inherent short channel effects limit their sensitivity, scalability and energy-efficiency. Therefore, to realize the true potential of the DMFET based biosensors, in this work, we propose a highly scalable, extremely sensitive and energy-efficient DM nanotube tunnel FET (NT-TFET) biosensor for label-free detection of biomolecules by modifying the structure of the conventional NT-TFET. The modified architecture facilitates the realization of a nanocavity at the source-channel tunneling junction and also provides stability to the immobilized biomolecules. We have performed an extensive analysis of the performance of the proposed DM NT-TFET biosensor in the presence of different representative target biomolecules characterized by different dielectric constants, and/or ionized charge densities using calibrated TCAD simulations. Our results indicate that the proposed DM NT-TFET exhibits an extremely high threshold voltage sensitivity ( SVth ) of 0.44, a high selectivity exceeding four orders of magnitude, ON-state current sensitivity ( SION ) of more than five orders of magnitude and could be a promising alternative to the conventional FET based dielectric modulated biosensors. Moreover, the sensitivity of the proposed DM NT-TFET could be further improved by utilizing alternate source materials with lower bandgap or by probing the transient response of the drain current and exploiting the difference in the settling time for different biomolecules with different dielectric constant ( κ ).

Plasmonic Biosensors Based on Deformed Graphene

Rapid, accurate, and label-free detection of biomolecules and chemical substances remains a challenge in healthcare. Optical biosensors have been considered as biomedical diagnostic tools required in numerous areas including the detection of viruses, food monitoring, diagnosing pollutants in the environment, global personalized medicine, and molecular diagnostics. In particular, the broadly emerging and promising technique of surface plasmon resonance has established to provide real-time and label-free detection when used in biosensing applications in a highly sensitive, specific, and cost-effective manner with small footprint platform. In this study we propose a novel plasmonic biosensor based on biaxially crumpled graphene structures, wherein plasmon resonances in graphene are utilized to detect variations in the refractive index of the sample medium. Shifts in the resonance wavelength of the plasmon modes for a given change in the RI of the surrounding analyte are calculated by investigating the optical response of crumpled graphene structures on different substrates using theoretical computations based on the finite element method combined with the semiclassical Drude model. The results reveal a high sensitivity of 4990 nm/RIU, corresponding to a large figure-of-merit of 20 for biaxially crumpled graphene structures on polystyrene substrates. We demonstrate that biaxially crumpled graphene exhibits superior sensing performance compared with a uniaxial structure. According to the results, crumpled graphene structures on a titanium oxide substrate can improve the sensor sensitivity by avoiding the damping effects of polydimethylsiloxane substrates. The enhanced sensitivity and broadband mechanical tunability of the biaxially crumpled graphene render it a promising platform for biosensing applications.

Fiber-Based Surface Plasmon Resonance Biosensor for Leptospira DNA Detection

Fiber-based surface plasmon resonance (SPR) sensors are the ideal configuration for rapid and label-free biomolecule detection. Gold-coated tapered optical fiber was used to excite the SPR mode that propagates at the metal–dielectric interface. By forming self-assembled monolayers (SAMs) of active chemical functional groups, the deoxyribonucleic acid (DNA) probe targeting the secY gene of Leptospira was immobilized onto the sensor surface. Red shifts in the SPR wavelengths were observed at different concentrations of leptospiral DNA target against the immobilized DNA probe due to the ability of plasmonic interaction to sensitively detect the binding of biomolecules on the sensor area. The developed sensor showed satisfactory linear responses at two target concentration ranges; low (1.0 fM to 1.0 pM) and high (0.1 nM to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$1.0~\mu \text{M}$ </tex-math></inline-formula> ), with the highest sensitivity of 1.22 nm per log M. The negative control test also revealed high sensor specificity toward the complementary DNA strand. This sensor will represent a significant step toward laboratory-free diagnosis of leptospirosis.

Performance assessment of cavity on source dual material split gate GaAs/InAs/Ge junctionless TFET for label-free detection of biomolecules

Performance assessment of cavity on source dual material split gate GaAs/InAs/Ge junctionless TFET for label-free detection of biomolecules