High Sensitive Biosensor Research Articles

Highly sensitive interfaces of graphene electrical-electrochemical vertical devices for on drop atto-molar DNA detection

The development of novel high-sensitivity DNA-based biosensors is beneficial, as these devices have applications in the identification of genetic risk factors, medical diagnostics, and environmental monitoring. Herein, we report on the first robust device capable of detecting DNA on a microliter drop with a zepto-molar (10−21) concentration. To accomplish this, we engineered an electrical-electrochemical vertical device (EEVD) that comprises a novel drain and source terminal in a short-circuited configuration, paired with an ideal non-polarizable reference electrode. Vertical electron transfer occurs perpendicularly to the graphene plane, while the electronic current flows through the graphene van der Waals (vdW) heterojunctions. Ferrocene adsorbed on graphene was strategically chosen as the vdW heterojunction redox component. Charge carrier insertion into the graphene makes the EEVD 10 times more sensitive than traditional graphene field-effect transistors. Interfacial potential changes were measured for single-stranded DNA detection with an unprecedented zepto-molar limit of detection.

A high sensitive and cost-effective disposable biosensor for adiponectin determination in real human serum samples

One of the adipose tissue cytokines, adiponectin is a newly defined adipocytokin, which is involved in insulin, glucose and adipocyte metabolisms. It has been determined that the amount of adiponectin in the circulatory system decreases in obese and type 2 diabetic patients. In addition to this decrease, many diseases such as heart diseases, high blood pressure, diabetes, joint diseases, high cholesterol, respiratory disease, gallbladder diseases are associated with obesity. Early detection of a decrease in the level of Adiponectin with a biosensor may be a new target for the prevention and treatment of cardiovascular diseases, immune disorder, joint disorders, especially obesity-related pathologies. In the scope of this study, poly ethylene terephthalate (PET) sheets covered with indium tin oxide (ITO), a unique transparent conductive material, was used as a working electrode which, introduced an extremely cheap and flexible material for this purpose. 3-Glycidoxypropyltrimethoxysilane (3-GOPS), an effective organosilane agent, produced a stable layer to immobilize anti-Adiponectin onto the working electrode surface. The immobilization of anti-Adiponectin onto ITO sheets were proved by the techniques, Fourier-transform infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM). The immunosensor prepared under optimal conditions gave a response in a wide range of concentrations (25 pg/mL–2500 pg/mL with a LOD value of 148 pg/mL) of Adiponectin. Finally, the designed biosensor was applied to real human serum samples and successful results were obtained.

Highly Sensitive Surface Plasmon Resonance Sensor Modified With 2D Ti₂C MXene for Solution Detection

Two-dimensional (2D) Ti2C MXene has great prospects in many fields of biotechnology and biosensing owning to their highly active 2D surfaces, in this work, we demonstrate a high sensitivity surface plasmon resonance (SPR) sensor modified by the 2D Ti2C nanosheets overlayer. Our experimental results show that the performances of the SPR sensor are closely related to the thickness of 2D Ti2C nanosheets, and the proposed design gives the wavelength sensitivity of 3579.6 nm/RIU, which are 79% higher than the SPR sensor without Ti2C overlayer. In addition, the Ti2C covered SPR sensor is capable of detecting low concentrations of heavy metal ions, our results show that the maximum concentrate sensitivities are 3.788 nm/ $\mu \text{g}$ /L, 5.308 nm/ $\mu \text{g}$ /L and 3.233 nm/ $\mu \text{g}$ /L for Pb2+, Cr2+ and Hg2+ ions, and the corresponding detection limits are 79.2 ng/L, 56.5 ng/L and 92.8 ng/L, which are lower than the international medical standards. Our results pave the way to realize high sensitivity biosensor and environmental pollution detection.

High-sensitive optoelectronic SPR biosensor based on Fano resonance in the integrated MIM junction and optical layers

Development of the miniaturized surface plasmon resonance (SPR) sensors with high sensitivity is required for biomedical sensing applications. In this regard, elimination of the optical detector and enhancement of sensitivity is an important step towards miniaturization of the traditional Kretschmann SPR sensors. In this study, we propose a compact high-sensitivity SPR biosensor with an electrical response based on Fano resonance in the metal–insulator–metal (MIM) junction integrated with the planar waveguide (PWG). The SPR excitation at the top metal of the MIM junction enhances the photoabsorption and hot electrons generation, which can produce photocurrent. We demonstrate that the coupling between the MIM junction SPR and PWG modes can result in modulation of output photocurrent by variation of analyte refractive index. The response of this sensor was calculated in detail and the results showed that the Fano-like profile appears in the photocurrent curve as well as the reflectivity curve. To evaluate the sensing performance of the proposed structure, the figure of merit (FOM) for the bulk sensitivity is predicated as 3.4×103 RIU−1, which is translated to change in the photocurrent of 33.5 μA by introducing the variation of 0.0001 in the refractive index of the analyte. Our results are highly useful for designing an integrated multi-function detector for future diagnoses and sensing applications.

Chip-based waveguides for high-sensitivity biosensing and super-resolution imaging

In this review, we introduce some chip-based waveguide biosensing and imaging techniques, which significantly reduce the complexity of the entire system. These techniques use a well-confined evanescent field to interact with the surrounding materials and achieve high sensitivity sensing and high signal-to-noise ratio (SNR) super-resolution imaging. The fabrication process of these chips is simple and compatible with conventional semiconductor fabrication methods, allowing high-yield production. Combined with recently developed chip-based light sources, these techniques offer the possibility of biosensing and super-resolution imaging based on integrated circuits.

Label-free detection of DNA by a dielectric modulated armchair-graphene nanoribbon FET based biosensor in a dual-nanogap setup.

A Double-Gate Armchair-Graphene Nanoribbon FET is proposed to realize a high-sensitive and small-size biosensor in order to detect DNA without high-cost and time-consuming labeling process. Two nanogap cavities open inside the top and bottom gate oxides by the method of sacrificed layer etching. When the DNA biomolecule is introduced to the nanogap cavity, the hybridization event which is actually the formation of a double-strand of DNA will occur thus electrically modulating the GNR channel leading to a change in the drain current. The important report of this research is about attained high sensitivity of the proposed biosensor for a vast spectrum of the DNA biological samples. It is worth noting that a DNA sequence by 23 nucleotides extracted from Neisseria gonorrhoeae can be detected as a special case. An extensive numerical approach has been applied in order to characterize the proposed biosensor. The suggested biosensor has been evaluated by solving Schrödinger equation )SE( with Non-Equilibrium Green Function (NEGF) method in the mode-space coupled into Poisson solver in a self-consistent manner assuming ballistic limit. Two different expressions of sensitivity in terms of the threshold voltage and current have been defined giving a good metric for the sensitivity analysis. The results revealed a relative sensitivity of 1mV/nm2 by a filled area by the DNA about 120nm2 showing the excellent superiority for the proposed biosensor as compared to other counterparts. The effective area of the proposed biosensor obtains 240nm2 which is very small in comparison with other reports highlighting high capability of the biosensor in the detection. It has been shown that the proposed biosensor can be implemented in ultra-scaling domain resulting in considerable increase in the sensitivity promising a potent and reliable candidate for high-sensitive and small-size biosensors. Also, the technical issues on designing the suggested biosensor have been investigated to achieve a useful guideline in detection and identification of the target DNAs.

High-Sensitivity, Quantified, Linear and Mediator-Free Resonator-Based Microwave Biosensor for Glucose Detection.

This article presents a high-sensitivity, quantified, linear, and mediator-free resonator-based microwave biosensor for glucose sensing application. The proposed biosensor comprises an air-bridge-type asymmetrical differential inductor (L) and a center-loaded circular finger-based inter-digital capacitor (C) fabricated on Gallium Arsenide (GaAs) substrate using advanced micro-fabrication technology. The intertwined asymmetrical differential inductor is used to achieve a high inductance value with a suitable Q-factor, and the centralized inter-digital capacitor is introduced to generate an intensified electric field. The designed microwave sensor is optimized to operate at a low resonating frequency that increases the electric field penetration depth and interaction area in the glucose sample. The microwave biosensor is tested with different glucose concentrations (0.3–5 mg/ml), under different ambient temperatures (10–50 °C). The involvement of advanced micro-fabrication technology effectively miniaturized the microwave biosensor (0.006λ0 × 0.005λ0) and enhanced its filling factor. The proposed microwave biosensor demonstrates a high sensitivity of 117.5 MHz/mgmL-1 with a linear response (r2 = 0.9987), good amplitude variation of 0.49 dB/mgmL-1 with a linear response (r2 = 0.9954), and maximum reproducibility of 0.78% at 2 mg/mL. Additionally, mathematical modelling was performed to estimate the dielectric value of the frequency-dependent glucose sample. The measured and analyzed results indicate that the proposed biosensor is suitable for real-time blood glucose detection measurements.

Plasmonic biosensor based on excellently absorbable adjustable plasmon-induced transparency in black phosphorus and graphene metamaterials

Both black phosphorus (BP) and graphene metamaterials support surface plasmon resonance that is very sensitive to the local change of dielectric properties in the system. We design a novel BP ribbons and graphene sheet hybrid structures based on tunable mid-infrared plasmon-induced transparency. The destructive interference of two excited state modes in the structure leads to a pronounced induced transparent window, and the excellent absorption of the two channels is obtained. The transmission characteristics of the hybrid structures are theoretical calculation, and the results are in good agreement with the numerical simulation curve. The dynamic adjustment function can be realized by adjusting the carrier density of BP and the Fermi level of graphene, and the excellent absorption performance not affected within the adjustment range. Moreover, we found that the optical phase is rapid flips at the plasmon resonance position. Therefore, a sensing medium layer is added on top of the structure to implement a high-sensitivity plasmonic biosensor. This work may provide potential applications to plasmonic devices based on two-dimensional metamaterial.

A Novel Design and Analysis of High-Sensitivity Biosensor Based on Nano-Cavity for Detection of Blood Component, Diabetes, Cancer and Glucose Concentration

In this study, a novel design of an optical biosensor based on resonance cavities and with high-resolution detection is proposed in a two-domains photonic crystal (2DPhCs) with free spectral range of around FSR = 630 nm. This sensor analyzes the internal components of the blood. It also detects a cancer patient from an ordinary person in the resonant wavelength range of 1.19760511 ~ 1.19760519 μm. Besides, it has the ability to detect the presence or absence of diabetes through human tear fluid with resonant wavelengths of 1.19760511 ~ 1.19760525 μm and measures the glucose concentration in urine. An analysis has been performed to determine the concentration of glucose in the normal state urine (0-15 mg/dL), urine with 0.625, 1.25, 2.5, 5 and 10 gm/dL of glucose in the wavelength range of 1.19760504 ~ 1.19760510 μm. Detection range is 0.2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-7</sup> RIU. The primary function of the biosensor is the resonant cavity. The average bandwidth value of the output resonant wavelength is at least equal to 0.195 nm. The quality factor of the proposed sensor at worst is 6141.56. The percentage of transmission power is between 90 % and 100 %. The total area of the biosensor is 100 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The sensitivity range is between 1250 nm/RIU and 10000 nm/RIU. The Figure of Merit (FOM) parameter at best is FOM = 48543 ± 118 RIU <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . Detections of the disease through three methods (blood, urine, and tears fluid samples) is an important advantage of the proposed structure.

D-type photonic crystal fiber sensor based on metal nanowire array

A design scheme of high-sensitivity metal nanowire-based D-type dual-core photonic crystal fiber local surface plasmon resonance biosensor is proposed. The sensor consists of a polished D-type dual-core photonic crystal fiber and a metal nanowire array. The coupling strength and phase matching of the core fundamental mode and the localized surface plasmon (LSPP) mode can be adjusted by small holes in the two cores. The small holes in the two cores can also control the position of the resonance wavelength. The coupling between the core fundamental mode and the LSPP mode can be promoted by increasing the nanowire radius and the array pitch. After numerical analysis of the sensor structure using the full vector finite element method (FEM), the performance of the metal silver nanowire array is optimal. Experiments show that the sensor has a sensitivity of 7000 nm/RIU when the detection range is 1.32–1.38. And the maximum spectral sensitivity can reach 16,000 nm/RIU. Compared with the traditional coating sensor, the performance of the sensor using the metal silver nanowire array has been significantly improved. The sensor has a good application prospect in the fields of biomolecule detection and pharmaceutical composition analysis.

Defects engineered 2D ultrathin cobalt hydroxide nanosheets as highly efficient electrocatalyst for non-enzymatic electrochemical sensing of glucose and l-cysteine

Engineering of nanomaterials with atomic defects has becoming an effective way to boost the sensitivity of the electrochemical biosensors but challenging. Herein, a rational, facile and in-situ strategy has been reported to obtain cobalt hydroxide nanosheets (VCo-Co(OH)2) with abundant cobalt vacancies. The cobalt defects greatly enriched electroactive sites and charge transfer rates, thereby delivered excellent electrocatalytic oxidation performance towards glucose and l-cysteine. The dynamic range and low limit of detection of glucose at VCo-Co(OH)2 electrodes were found as 0.4 μM–8.23 mM and 295 nM respectively. Besides, VCo-Co(OH)2 electrodes accurately sensed the l-cysteine with lowest detection limit (76.5 nM), and broad linear sensing range (200 nM-1.94 mM), which are better than the performance of defect-free Co(OH)2 electrodes, evidence that construction of cobalt vacancy significantly boosted the electrocatalysis. Importantly, fabricated sensors had excellent interference immunity against the many biomolecules, owns good stability and reproducibility. Present work not only proposed a novel and simplistic approach to prepare the metal hydroxides with copious metal cation vacancies for electrocatalysis but also provides economical, precise, high-sensitive and disposable biosensors for clinical analysis glucose and l-cysteine.

Ion Current Rectification in Extra-Long Nanofunnels

Nanofluidic systems offer new functionalities for the development of high sensitivity biosensors, but many of the interesting electrokinetic phenomena taking place inside or in the proximity of nanostructures are still not fully characterized. Here, to better understand the accumulation phenomena observed in fluidic systems with asymmetric nanostructures, we study the distribution of the ion concentration inside a long (more than 90 µm) micrometric funnel terminating with a nanochannel. We show numerical simulations, based on the finite element method, and analyze how the ion distribution changes depending on the average concentration of the working solutions. We also report on the effect of surface charge on the ion distribution inside a long funnel and analyze how the phenomena of ion current rectification depend on the applied voltage and on the working solution concentration. Our results can be used in the design and implementation of high-performance concentrators, which, if combined with high sensitivity detectors, could drive the development of a new class of miniaturized biosensors characterized by an improved sensitivity.

(Invited) Plasmon Enhanced IR Spectroscopy and Electrochemistry

The localized surface plasmon resonance (LSPR) arises from the collective oscillation of conduction electrons of metal nanostructures which can be used to monitor recognition events of biomolecules at single nanoparticles1. The enhanced electric field around the nanostructures due to LSPR will significantly enhance the Raman scattering, fluorescence and IR spectra, which enable the realization of single molecule detection. In addition, the LSPR will excite high-energy electron-hole pair (referred to as “hot electrons” and “hot holes”) emerging on metal surface. The energetic charges will considerably affect the electrochemical reactions occurring at the nanoparticles. When the plasmonic metallic nanostructures are coupled to other substrates, for example, the semiconductor (i.e., TiO2, MoS2), the plasmon-excited hot electron-hole at nanoparticle surface can communicate with the conductance and valence bands of the semiconductors, resulting in variation in electro/photocatalytic activity. In this talk, we will start with the LSPR enhanced IR for biosensing.1 Then, we will show how the LSPR accelerates electrochemical reactions of electroactive biomolecules such as glucose on gold nanoparticles and hydrogen evolution reaction at molybdenum disulphide nanosheets.2 Based on the plasmonics accelerated electrochemical reactions (PAER), high sensitive electrochemical biosensors for detection of glucose and other electroactive biomolecules have been constructed.

Design 5.0 µm Gap Aluminium Interdigitated Electrode for Sensitive pH Detection

The aim of the research study to design high sensitive biosensor for medical applications. IDE pattern was designed using AutoCAD software with 5 µm ginger gap. The fabrication process was done using a conventional photolithography process and standard CMOS process. The fabricated electrode was physically characterized using a low power microscope (LPM) and a high power microscope (HPM). The electrically validated through I-V measurements and chemically tested with different pH buffer solutions. Al IDE was well fabricated with 0.1 µm tolerance between the design mask and fabricated IDEs. Electrical measurements confirmed that IDE was well fabricated without any shortage and results of similar IDE samples were confirmed that the repeatability of the device. The extremely small current variations in nano ampere range were quantitatively detected using an extra small volume of 2 µl for different pH buffer solutions. It is confirmed that IDEs are sensitive in both alkali and hydroxyl ions medium.

High-sensitivity biosensor for identification of protein based on terahertz Fano resonance metasurfaces

Terahertz metasurface biosensors have gained significant attention in biological field due to its label-free, real-time and in-situ detection properties. In this paper, a planar array of Fano asymmetric split ring resonators (ASRs) fabricated on 25μm flexible polyimide substrate was proposed for new terahertz metasurface biosensors. It is shown that 160 GHz/RIU and 240 GHz/RIU refractive index sensitivity can be severally obtained near 0.81 and 1.13 THz transmission dips of the proposed system. Correspondingly, for biosensor samples that protein A/G, A/G + IgG were spotted on ASRs surface in our experiment, shifts of 8.9 GHz and 11.7 GHz, 17.6 GHz and 52.9 GHz toward low frequency were observed, respectively. These results illustrate high-sensitivity and label-free detection of proteins, implying a new feasible way of sensing in terahertz domain.

High Sensitive Biosensors Based on the Coupling Between Surface Plasmon Polaritons on Titanium Nitride and a Planar Waveguide Mode.

High sensitivity biosensors based on the coupling of surface plasmon polaritons on titanium nitride (TiN) and a planar waveguide mode were built; they were proved by sensing three different media: air, water and dried egg white; sensors described here could be useful for sensing materials with a refractive index between 1.0 and 1.6; in particular, materials of biological interest with a refractive index in the range 1.3–1.6, like those containing biotin and/or streptavidin. They were built by depositing Nb2O5/SiO2/TiN multilayer structures on the flat surface of D-shaped sapphire prisms by using the dc magnetron sputtering technique. Attenuated total reflection (ATR) experiments in the Kretschmann configuration were accomplished for the air/TiN/Prism and S/Nb2O5/SiO2/TiN/Prism structures, S being the sample or sensing medium. ATR spectra for plasmons at the TiN/air interface showed a broad absorption band for angles of incidence between 36 and 85°, with full width at half maximum (FWHM) of approximately 40°. For the S/Nb2O5/SiO2/TiN/Prism structures, ATR spectra showed a sharp reflectivity peak, within the broad plasmonic absorption band, which was associated with Fano resonances. The angular position and FWHM of the Fano resonances strongly depend on the refractive index of the sensing medium. ATR spectra were fitted by using the transfer-matrix method. Additionally, we found that angular sensitivity and figure of merit increase with increasing the refractive index of the sensing medium.

A label-free fluorescence biosensor based on a bifunctional MIL-101(Fe) nanozyme for sensitive detection of choline and acetylcholine at nanomolar level

A label-free and high sensitive fluorescence biosensor for the detection of choline and acetylcholine (ACh) was developed based on the MIL-101(Fe) nanozyme with dual functions of mimetic peroxidase and fluorescent emission. This fluorescence sensing strategy involves the reaction of acetylcholinesterase (AChE) catalyzing the hydrolysis of ACh into choline that is in turn oxidized by choline oxidase (ChOx) to generate H2O2, and the as-produced H2O2 is decomposed into highly reactive hydroxyl radicals under the catalysis of MIL-101(Fe) nanozyme, thereby the non-fluorescent organic ligand terephthalic acid of MIL-101(Fe) is oxidized by hydroxyl radicals to form a highly fluorescent 2-hydroxy terephthalic acid. By virtue of this finding, the label-free detection of choline and ACh via multienzyme cascade reaction was realized with low detection limits of 20.0 nM and 8.9 nM, respectively. Moreover, the practicality of the developed bifunctional MIL-101(Fe)-based sensing strategy was successfully validated through the detection of choline in milk and ACh in human plasma. This proposed assay not only exhibited high sensitivity and selectivity towards choline and ACh, but also simplified the sensing systems, reduced the detection cost, and avoided the potential risks caused by the fluorescent reagents, which opened a green avenue for the analysis of complex biological samples.

High-Q Fano resonance based on degenerate modes in a single dielectric point-defect photonic crystal cavity with x–y asymmetry

We designed multiple degenerate modes in a single-point-defect photonic crystal cavity with x–y-asymmetry to act as bright and dark modes to produce Fano resonances. Under suitable operating parameters, the power-flows in incident-direction for two degenerated modes cancel each other, resulting high Q-factors for Fano modes. Extremely-high Q-factor of Fano resonances exceeding 108 with transmittance larger than 0.867 is obtained based on modes with Q-factors less than 104, and in further exploration, the Q-factor can reach 3 × 1010. This method provides a basis to design compact, high-Q Fano devices for extremely high-sensitivity biosensing, switching and lasing.

Three-dimensional cavity-coupled metamaterials for plasmonic color and real-time colorimetric biosensors.

Plasmonic structure color has significant potential for visual biochemical sensing by simple instrumentation or even naked eye detection. Herein, we present a visual and real-time sensing strategy for refraction index sensing and detection of the biotin-avidin system based on three-dimensional cavity-coupled metamaterials. These metamaterials composed of a top array of gold disks, aluminium pillars and a bottom reflection film of aluminium have structures similar to the metal-insulator-metal structure. The insulating layer comprises air-gap cavities that are easily filled with gaseous or liquid dielectrics. Therefore, analytes can permeate into the nano-scale cavities and produce strong light-matter interactions. The sensor shows that any tiny change in the refraction index will induce a significant color variation and the sensitivity reaches 683.5 nm per refraction index unit with a figure of merit of 3.5. The color of the metamaterials changes from rose-red to violet and then loden after a monomolecular layer of thiolated biotin and streptavidin bind to the surface of the nanostructure successively. This sensing strategy offers new opportunities for the convenient detection of proteins, nucleic acids, and lipids.

Introducing waveguide loss: Another way to realize a high-sensitivity microring biosensor

Real-time and high-sensitivity biosensors are urgently needed in biochemistry. As one of the candidates, silicon-on-insulator (SOI) sensors exhibits excellent performances. However, there are still some limitations to hinder them to be applied to much wider scenarios. Fabrication tolerance is also required for the generalization of these micro- or nano-structure. In this work, we demonstrate an SOI waveguide biosensor for biochemical sensing with high sensitivity of 1.88 × 105 dB/RIU. Because of the compact structure and low demand for accuracy of fabrication, this device possesses better applicability and reliability.